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Phenotypes associated with this allele
Allele Symbol
Allele Name
Allele ID
Tg(Camk2a-tTA)1Mmay
transgene insertion 1, Mark Mayford
MGI:2179066
Summary 62 genotypes
Jump to Allelic Composition Genetic Background Genotype ID
cn1
Psmc1tm1Maye/Psmc1tm1Maye
Tg(Camk2a-tTA)1Mmay/0
Tg(tetO-cre)1Lin/0
involves: 129 * C57BL/6 * CD-1 MGI:3809773
cn2
Gabrg2tm2Spet/Gabrg2+
Tg(Camk2a-tTA)1Mmay/0
Tg(tetO-cre)LC1Bjd/0
involves: 129S1/Sv * 129X1/SvJ * BALB/c * C57BL/6 MGI:5474679
cn3
Grin1tm1Rsp/Grin1tm1Rsp
Tg(Camk2a-tTA)1Mmay/?
Tg(tetO-cre)LC1Bjd/?
involves: 129S1/Sv * 129X1/SvJ * BALB/c * C57BL/6 MGI:3708939
cn4
Npy1rtm1.1Ceva/Npy1rtm1.1Ceva
Tg(Camk2a-tTA)1Mmay/0
Tg(tetO-cre)LC1Bjd/0
involves: 129S1/Sv * 129X1/SvJ * BALB/c * C57BL/6 * SJL MGI:5307910
cx5
Apba2tm1Tsuz/Apba2tm1Tsuz
Tg(Camk2a-tTA)1Mmay/0
Tg(tetO-APBA2,-lacZ)1Ito/0
B6.Cg-Apba2tm1Tsuz Tg(Camk2a-tTA)1Mmay Tg(tetO-APBA2,-lacZ)1Ito MGI:4418496
cx6
Tg(Camk2a-tTA)1Mmay/?
Tg(tetO-CALY)5Cber/?
B6.Cg-Tg(Camk2a-tTA)1Mmay Tg(tetO-CALY)5Cber MGI:5429538
cx7
Tg(Camk2a-tTA)1Mmay/0
Tg(tetO-Gnas)1593Mpke/0
B6.Cg-Tg(Camk2a-tTA)1Mmay Tg(tetO-Gnas)1593Mpke MGI:4843272
cx8
Tg(Camk2a-tTA)1Mmay/0
Tg(tetO-APPSwInd)107Dbo/0
(FVB/NJ x B6.Cg-Tg(tetO-APPSwInd)107Dbo Tg(Camk2a-tTA)1Mmay)F1 MGI:5478560
cx9
Bace1tm1Pcw/Bace1+
Tg(Camk2a-tTA)1Mmay/0
Tg(tetO-CDK5R1/GFP)337Lht/0
involves: 129S1/Sv * 129X1/SvJ * C57BL/6J MGI:5634918
cx10
Tg(Camk2a-tTA)1Mmay/?
Tg(tetO-DRD2)2-5Kndl/?
involves: 129S6/SvEvTac * C57BL/6 * CBA MGI:5693761
cx11
Tg(Camk2a-tTA)1Mmay/0
Tg(tetO-Comt)1Kndl/0
involves: 129S6/SvEvTac * C57BL/6J MGI:5694075
cx12
Tg(Camk2a-tTA)1Mmay/0
Tg(tetO-MAPT*P301L)#Kha/0
involves: 129S6/SvEvTac * FVB/N MGI:5558945
cx13
Tg(Camk2a-tTA)1Mmay/?
Tg(tetO-MAPT*P301L)#Kha/?
involves: 129S6/SvEvTac * FVB/N MGI:4819951
cx14
Tg(Camk2a-tTA)1Mmay/0
Tg(tetO-Csnk1d)#Mfla/0
involves: 129/Sv * C57BL/6 MGI:4452245
cx15
Tg(Camk2a-tTA)1Mmay/0
Tg(tetO-MAPT*P301L)#Kha/0
involves: 129/Sv * C57BL/6 * CBA * FVB/N MGI:5438795
cx16
Lrrk2tm1.1Cai/Lrrk2+
Tg(Camk2a-tTA)1Mmay/0
Tg(tetO-SNCA*A53T)E2Cai/0
involves: 129X1/SvJ * C57BL/6 MGI:4421006
cx17
Lrrk2tm1.1Cai/Lrrk2tm1.1Cai
Tg(Camk2a-tTA)1Mmay/0
Tg(tetO-SNCA*A53T)E2Cai/0
involves: 129X1/SvJ * C57BL/6 MGI:4421016
cx18
Tg(Camk2a-tTA)1Mmay/0
Tg(tetO-SNCA*A53T)33Vle/0
involves: C3H/HeH * C57BL/6 MGI:5289971
cx19
Tg(Camk2a-tTA)1Mmay/0
Tg(tetO-SNCA)7Vle/0
involves: C3H/HeH * C57BL/6 MGI:5289970
cx20
Tg(Camk2a-tTA)1Mmay/0
Tg(tetO-APPSwInd)885Dbo/0
Tg(tetO-LRRK2*G2019S)E3Cai/0
involves: C3H/HeJ * C57BL/6 MGI:4421004
cx21
Tg(Camk2a-tTA)1Mmay/0
Tg(tetO-APPSwInd)107Dbo/0
involves: C3H/HeJ * C57BL/6 * CBA MGI:3709152
cx22
Tg(Camk2a-tTA)1Mmay/0
Tg(tetO-APPSwInd)18Dbo/0
involves: C3H/HeJ * C57BL/6 * CBA MGI:3709154
cx23
Tg(Camk2a-tTA)1Mmay/0
Tg(tetO-APPSwInd)102Dbo/0
involves: C3H/HeJ * C57BL/6 * CBA MGI:3709182
cx24
Tg(Camk2a-tTA)1Mmay/0
Tg(tetO-APPSwInd)885Dbo/0
involves: C3H/HeJ * C57BL/6 * CBA MGI:3696400
cx25
Tg(Camk2a-tTA)1Mmay/0
Tg(tetO-TARDBP*)4Vle/0
involves: C3H/HeJ * C57BL/6J MGI:5448853
cx26
Tg(Camk2a-tTA)1Mmay/0
Tg(tetO-TARDBP)12Vle/0
involves: C3H/HeJ * C57BL/6J MGI:5448852
cx27
Tg(Camk2a-tTA)1Mmay/0
Tg(tetO-LRRK2*)D10Cai/0
Tg(tetO-SNCA*A53T)E2Cai/0
involves: C57BL/6 MGI:4420998
cx28
Tg(Camk2a-tTA)1Mmay/0
Tg(tetO-SNCA)1Cai/0
involves: C57BL/6 MGI:4421057
cx29
Tg(Camk2a-tTA)1Mmay/0
Tg(tetO-LRRK2*)D10Cai/0
involves: C57BL/6 MGI:4420997
cx30
Tg(Camk2a-tTA)1Mmay/0
Tg(tetO-LRRK2)C77Cai/0
Tg(tetO-SNCA*A53T)E2Cai/0
involves: C57BL/6 MGI:4420996
cx31
Tg(Camk2a-tTA)1Mmay/0
Tg(tetO-LRRK2)C77Cai/0
involves: C57BL/6 MGI:4420995
cx32
Tg(Camk2a-tTA)1Mmay/0
Tg(tetO-S100a10)1Pggd/0
involves: C57BL/6 MGI:3776630
cx33
Tg(Camk2a-tTA)1Mmay/0
Tg(tetO-LRRK2)C7874Cai/0
involves: C57BL/6 MGI:4421001
cx34
Tg(Camk2a-tTA)1Mmay/0
Tg(tetO-LRRK2)C7874Cai/0
Tg(tetO-SNCA*A53T)E2Cai/0
involves: C57BL/6 MGI:4421002
cx35
Tg(Camk2a-tTA)1Mmay/0
Tg(tetO-SNCA*A53T)E2Cai/0
involves: C57BL/6 MGI:4421003
cx36
Tg(Camk2a-tTA)1Mmay/0
Tg(tetO-LRRK2*G2019S)E3Cai/0
Tg(tetO-SNCA*A53T)E2Cai/0
involves: C57BL/6 MGI:4421000
cx37
Tg(Camk2a-tTA)1Mmay/0
Tg(tetO-LRRK2*G2019S)E3Cai/0
Tg(tetO-SNCA)1Cai/0
involves: C57BL/6 MGI:4421005
cx38
Tg(Camk2a-tTA)1Mmay/0
Tg(tetO-LRRK2*G2019S)E3Cai/0
involves: C57BL/6 MGI:4420999
cx39
Tg(Camk2a-tTA)1Mmay/0
Tg(tetO-SNCA)0Olri/0
involves: C57BL/6 MGI:5512702
cx40
Tg(Camk2a-tTA)1Mmay/0
Tg(tetO-MAPT*K280,-luc)#Eman/0
involves: C57BL/6 MGI:5554193
cx41
Tg(Camk2a-tTA)1Mmay/0
Tg(tetO-MAPT*K280*I277P*I308P,-luc)#Eman/0
involves: C57BL/6 MGI:5554195
cx42
Tg(Camk2a-tTA)1Mmay/0
Tg(tetO-COX8A/EYFP)1Ksn/0
involves: C57BL/6 MGI:3700230
cx43
Tg(Camk2a-tTA)1Mmay/0
Tg(tetO-DRD3)3-10Kndl/0
involves: C57BL/6 * CBA MGI:5694057
cx44
Tg(Camk2a-tTA)1Mmay/0
Tg(tetO-HTT*94Q,-lacZ)1Rhn/0
involves: C57BL/6 * CBA MGI:3851446
cx45
Tg(Camk2a-tTA)1Mmay/0
Tg(tetO-DISC1*)1001Plet/0
involves: C57BL/6 * CBA * SJL MGI:3838963
cx46
Tg(Camk2a-tTA)1Mmay/0
Tg(tetO-COX8A/PstI*)1Ctm/0
involves: C57BL/6 * CBA * SJL MGI:5316005
cx47
Tg(Camk2a-tTA)1Mmay/0
Tg(tetO-Mtor*)#Atai/0
involves: C57BL/6 * DBA/2 * ICR MGI:5634716
cx48
Tg(Camk2a-tTA)1Mmay/0
Tg(tetO-CDK5R1/GFP)337Lht/0
involves: C57BL/6J MGI:3653709
cx49
Tg(Camk2a-tTA)1Mmay/0
Tg(tetO-Rai1,-EGFP)463Walz/0
involves: C57BL/6J * CBA/J MGI:5555966
cx50
Tg(Camk2a-tTA)1Mmay/0
Tg(tetO-Rai1,-EGFP)479Walz/0
involves: C57BL/6J * CBA/J MGI:5555967
cx51
Tg(Camk2a-tTA)1Mmay/0
Tg(tetO-LMNB1)AF1Yfu/0
involves: FVB MGI:5491208
cx52
Tg(Camk2a-tTA)1Mmay/0
Tg(tetO-MAPT*P301L)#Kha/0
involves: FVB/N MGI:5511058
cx53
Tg(Camk2a-tTA)1Mmay/0
Tg(tetO-LRRK2)1Cai/0
Not Specified MGI:4414670
cx54
Tg(Camk2a-tTA)1Mmay/0
Tg(tetO-LRRK2*G2019S)1Cai/0
Not Specified MGI:4414669
tg55
Tg(Camk2a-tTA)1Mmay/0 (B6.Cg-Tg(Camk2a-tTA)1Mmay x 129X1/SvJ)F1 MGI:5438789
tg56
Tg(Camk2a-tTA)1Mmay/0 (B6.Cg-Tg(Camk2a-tTA)1Mmay x C3H/HeJ)F1 MGI:5438785
tg57
Tg(Camk2a-tTA)1Mmay/0 (B6.Cg-Tg(Camk2a-tTA)1Mmay x C3H/HeJ)F1 x C3H/HeJ MGI:5438807
tg58
Tg(Camk2a-tTA)1Mmay/0 (B6.Cg-Tg(Camk2a-tTA)1Mmay x CBA/J)F1 MGI:5438788
tg59
Tg(Camk2a-tTA)1Mmay/0 (B6.Cg-Tg(Camk2a-tTA)1Mmay x DBA/1J)F1 MGI:5438790
tg60
Tg(Camk2a-tTA)1Mmay/0 (B6.Cg-Tg(Camk2a-tTA)1Mmay x FVB/NJ)F1 MGI:5438792
tg61
Tg(Camk2a-tTA)1Mmay/0 involves: C3H/HeJ * C57BL/6 * CBA MGI:5438801
tg62
Tg(Camk2a-tTA)1Mmay/? B6.Cg-Tg(Camk2a-tTA)1Mmay MGI:5438794


Genotype
MGI:3809773
cn1
Allelic
Composition
Psmc1tm1Maye/Psmc1tm1Maye
Tg(Camk2a-tTA)1Mmay/0
Tg(tetO-cre)1Lin/0
Genetic
Background
involves: 129 * C57BL/6 * CD-1
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Psmc1tm1Maye mutation (0 available); any Psmc1 mutation (7 available)
Tg(Camk2a-tTA)1Mmay mutation (6 available)
Tg(tetO-cre)1Lin mutation (1 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
mortality/aging
• die at 3-4 months of age (J:138991)
• die at 3-4 months of age (J:138991)

growth/size/body
• subtle growth retardation starting 5 weeks of age and becoming statistically significant by 8 weeks (J:138991)
• subtle growth retardation starting 5 weeks of age and becoming statistically significant by 8 weeks (J:138991)

behavior/neurological
• lack interest in locating food at 3-4 months of age (J:138991)
• lack interest in locating food at 3-4 months of age (J:138991)
• significantly more anxious in open-field analysis at 6 weeks (J:138991)
• significantly more anxious in open-field analysis at 6 weeks (J:138991)
• obvious spatial learning deficits in the Morris water maze at 8 weeks (J:138991)
• obvious spatial learning deficits in the Morris water maze at 8 weeks (J:138991)

nervous system
• expansion of the ventricular cavities accompanying atrophy of the forebrain (J:138991)
• expansion of the ventricular cavities accompanying atrophy of the forebrain (J:138991)
• extensive neuronal loss by 8 weeks (J:138991)
• extensive neuronal loss by 8 weeks (J:138991)
• significant progressive atrophy of the forebrain (J:138991)
• significant progressive atrophy of the forebrain (J:138991)
• extensive gliosis as a result of the neuronal damage (J:138991)
• extensive gliosis as a result of the neuronal damage (J:138991)
• numerous eosinophilic intraneuronal paranuclear inclusions, containing ubiquitin, alpha-synuclein, and p62, similar to Lewy bodies (J:138991)
• numerous eosinophilic intraneuronal paranuclear inclusions, containing ubiquitin, alpha-synuclein, and p62, similar to Lewy bodies (J:138991)
• neurodegeneration was evident in neurons expressing Tg(Camk2a-tTA)1Mmay in forebrain, hippocampus, striatum, and amygdala (J:138991)
• neurodegeneration was evident in neurons expressing Tg(Camk2a-tTA)1Mmay in forebrain, hippocampus, striatum, and amygdala (J:138991)

cellular




Genotype
MGI:5474679
cn2
Allelic
Composition
Gabrg2tm2Spet/Gabrg2+
Tg(Camk2a-tTA)1Mmay/0
Tg(tetO-cre)LC1Bjd/0
Genetic
Background
involves: 129S1/Sv * 129X1/SvJ * BALB/c * C57BL/6
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Gabrg2tm2Spet mutation (0 available); any Gabrg2 mutation (5 available)
Tg(Camk2a-tTA)1Mmay mutation (6 available)
Tg(tetO-cre)LC1Bjd mutation (2 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
behavior/neurological
• induced by pentylenetetrazil in mice treated with doxycycline treatment between conception and P21 or not treated with doxycycline at all (J:194736)
• induced by pentylenetetrazil compared with Gabrg2tm2Spet heterozygotes (J:194736)
• doxycycline treatment between conception and P21 increased the time to first clonic seizure compared with mice not treated with doxycycline (J:194736)
• however, no seizure kindling effect is observed (J:194736)
• induced by pentylenetetrazil in mice treated with doxycycline treatment between conception and P21 or not treated with doxycycline at all (J:194736)
• induced by pentylenetetrazil compared with Gabrg2tm2Spet heterozygotes (J:194736)
• doxycycline treatment between conception and P21 increased the time to first clonic seizure compared with mice not treated with doxycycline (J:194736)
• however, no seizure kindling effect is observed (J:194736)

nervous system
• induced by pentylenetetrazil in mice treated with doxycycline treatment between conception and P21 or not treated with doxycycline at all (J:194736)
• induced by pentylenetetrazil compared with Gabrg2tm2Spet heterozygotes (J:194736)
• doxycycline treatment between conception and P21 increased the time to first clonic seizure compared with mice not treated with doxycycline (J:194736)
• however, no seizure kindling effect is observed (J:194736)
• induced by pentylenetetrazil in mice treated with doxycycline treatment between conception and P21 or not treated with doxycycline at all (J:194736)
• induced by pentylenetetrazil compared with Gabrg2tm2Spet heterozygotes (J:194736)
• doxycycline treatment between conception and P21 increased the time to first clonic seizure compared with mice not treated with doxycycline (J:194736)
• however, no seizure kindling effect is observed (J:194736)




Genotype
MGI:3708939
cn3
Allelic
Composition
Grin1tm1Rsp/Grin1tm1Rsp
Tg(Camk2a-tTA)1Mmay/?
Tg(tetO-cre)LC1Bjd/?
Genetic
Background
involves: 129S1/Sv * 129X1/SvJ * BALB/c * C57BL/6
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Grin1tm1Rsp mutation (1 available); any Grin1 mutation (18 available)
Tg(Camk2a-tTA)1Mmay mutation (6 available)
Tg(tetO-cre)LC1Bjd mutation (2 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
nervous system
• complete loss of NMDAR-mediated long term potential at dentate gyrus synapses (J:119834)
• however, long term potentiation at Schaffer collateral-CA1 synapses is similar to wild-type mice despite residual Cre activity in CA1 pyramidal cells (J:119834)
• complete loss of NMDAR-mediated long term potential at dentate gyrus synapses (J:119834)
• however, long term potentiation at Schaffer collateral-CA1 synapses is similar to wild-type mice despite residual Cre activity in CA1 pyramidal cells (J:119834)

behavior/neurological
• mice exhibit impaired spatial working memory but normal spatial reference memory in a 3 from 6 radial arm maze task (J:119834)
• mice exhibit impaired spatial working memory but normal spatial reference memory in a 3 from 6 radial arm maze task (J:119834)




Genotype
MGI:5307910
cn4
Allelic
Composition
Npy1rtm1.1Ceva/Npy1rtm1.1Ceva
Tg(Camk2a-tTA)1Mmay/0
Tg(tetO-cre)LC1Bjd/0
Genetic
Background
involves: 129S1/Sv * 129X1/SvJ * BALB/c * C57BL/6 * SJL
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Npy1rtm1.1Ceva mutation (0 available); any Npy1r mutation (5 available)
Tg(Camk2a-tTA)1Mmay mutation (6 available)
Tg(tetO-cre)LC1Bjd mutation (2 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
adipose tissue
• Background Sensitivity: in doxycycline-treated mice raised by FVB/J (J:180396)
• however, doxycycline-treated mice raised by C57BL/6J dams exhibit normal white adipose tissue weight (J:180396)
• Background Sensitivity: in doxycycline-treated mice raised by FVB/J (J:180396)
• however, doxycycline-treated mice raised by C57BL/6J dams exhibit normal white adipose tissue weight (J:180396)
• Background Sensitivity: in doxycycline-treated mice raised by FVB/J (J:180396)
• however, doxycycline-treated mice raised by C57BL/6J dams exhibit normal white adipose tissue weight (J:180396)
• Background Sensitivity: in doxycycline-treated mice raised by FVB/J (J:180396)
• however, doxycycline-treated mice raised by C57BL/6J dams exhibit normal white adipose tissue weight (J:180396)
• Background Sensitivity: visceral, epididymal and subcutaneous white adipose tissue in doxycycline-treated mice raised by FVB/J (J:180396)
• however, doxycycline-treated mice raised by C57BL/6J dams exhibit normal white adipose tissue weight (J:180396)
• Background Sensitivity: visceral, epididymal and subcutaneous white adipose tissue in doxycycline-treated mice raised by FVB/J (J:180396)
• however, doxycycline-treated mice raised by C57BL/6J dams exhibit normal white adipose tissue weight (J:180396)

homeostasis/metabolism
• Background Sensitivity: in doxycycline-treated mice raised by FVB/J (J:180396)
• however, doxycycline-treated mice raised by C57BL/6J dams exhibit normal leptin levels (J:180396)
• Background Sensitivity: in doxycycline-treated mice raised by FVB/J (J:180396)
• however, doxycycline-treated mice raised by C57BL/6J dams exhibit normal leptin levels (J:180396)
• Background Sensitivity: in doxycycline-treated mice raised by FVB/J (J:180396)
• however, doxycycline-treated mice raised by C57BL/6J dams exhibit normal leptin levels (J:180396)
• Background Sensitivity: in doxycycline-treated mice raised by FVB/J (J:180396)
• however, doxycycline-treated mice raised by C57BL/6J dams exhibit normal leptin levels (J:180396)

behavior/neurological
• Background Sensitivity: in an elevated plus maze and open field test, doxycycline-treated mice raised by FVB/J dams exhibit increased anxiety-related behaviors compared with similarly fostered control mice (J:180396)
• however, doxycycline-treated mice fostered by C57BL/6J dams exhibit normal anxiety (J:180396)
• Background Sensitivity: in an elevated plus maze and open field test, doxycycline-treated mice raised by FVB/J dams exhibit increased anxiety-related behaviors compared with similarly fostered control mice (J:180396)
• however, doxycycline-treated mice fostered by C57BL/6J dams exhibit normal anxiety (J:180396)
• doxycycline-treated mice raised by C57BL/6J dams exhibit decreased total distance traveled in an open field compared with control mice and doxycycline-treated mice raised by FVB/J dams (J:180396)
• doxycycline-treated mice raised by C57BL/6J dams exhibit decreased total distance traveled in an open field compared with control mice and doxycycline-treated mice raised by FVB/J dams (J:180396)

growth/size/body
• after doxycycline treatment at P41 and P48, mice raised by FVB/J dams, and to a lesser extent raised by C57BL/6J dams, exhibit slower body weight gain compared with control mice (J:180396)
• after doxycycline treatment at P41 and P48, mice raised by FVB/J dams, and to a lesser extent raised by C57BL/6J dams, exhibit slower body weight gain compared with control mice (J:180396)

integument
• Background Sensitivity: in doxycycline-treated mice raised by FVB/J (J:180396)
• however, doxycycline-treated mice raised by C57BL/6J dams exhibit normal white adipose tissue weight (J:180396)
• Background Sensitivity: in doxycycline-treated mice raised by FVB/J (J:180396)
• however, doxycycline-treated mice raised by C57BL/6J dams exhibit normal white adipose tissue weight (J:180396)




Genotype
MGI:4418496
cx5
Allelic
Composition
Apba2tm1Tsuz/Apba2tm1Tsuz
Tg(Camk2a-tTA)1Mmay/0
Tg(tetO-APBA2,-lacZ)1Ito/0
Genetic
Background
B6.Cg-Apba2tm1Tsuz Tg(Camk2a-tTA)1Mmay Tg(tetO-APBA2,-lacZ)1Ito
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Apba2tm1Tsuz mutation (0 available); any Apba2 mutation (1 available)
Tg(Camk2a-tTA)1Mmay mutation (6 available)
Tg(tetO-APBA2,-lacZ)1Ito mutation (0 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
behavior/neurological
• with or without DOX administration, adult mice bury significantly more marbles than null mice in the marble burying test (J:148481)
• DOX administration to parental mice results in progeny which bury significantly fewer marbles than wild-type mice in the marble burying test (J:148481)
• with or without DOX administration, adult mice bury significantly more marbles than null mice in the marble burying test (J:148481)
• DOX administration to parental mice results in progeny which bury significantly fewer marbles than wild-type mice in the marble burying test (J:148481)
• without DOX administration mice displace significantly more food pellets from a tube than null mice in a burrowing test (J:148481)
• without DOX administration mice displace significantly more food pellets from a tube than null mice in a burrowing test (J:148481)
• with or without DOX administration mice have decreased locomotor activity (J:148481)
• with or without DOX administration mice have decreased locomotor activity (J:148481)
• without DOX administration total number of resident social interactions with intruder mice are significantly increased compared to null mice in a resident-intruder test (J:148481)
• without DOX administration total number of resident social interactions with intruder mice are significantly increased compared to null mice in a resident-intruder test (J:148481)




Genotype
MGI:5429538
cx6
Allelic
Composition
Tg(Camk2a-tTA)1Mmay/?
Tg(tetO-CALY)5Cber/?
Genetic
Background
B6.Cg-Tg(Camk2a-tTA)1Mmay Tg(tetO-CALY)5Cber
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tg(Camk2a-tTA)1Mmay mutation (6 available)
Tg(tetO-CALY)5Cber mutation (1 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
behavior/neurological
• greater distance traveled and more exploration of the center in an open field test (J:181086)
• increased time spent in the open box in a light/dark box apparatus (J:181086)
• enter the open arm of an elevated plus maze more frequently than controls and travel greater distances in the apparatus (J:181086)
• greater distance traveled and more exploration of the center in an open field test (J:181086)
• increased time spent in the open box in a light/dark box apparatus (J:181086)
• enter the open arm of an elevated plus maze more frequently than controls and travel greater distances in the apparatus (J:181086)




Genotype
MGI:4843272
cx7
Allelic
Composition
Tg(Camk2a-tTA)1Mmay/0
Tg(tetO-Gnas)1593Mpke/0
Genetic
Background
B6.Cg-Tg(Camk2a-tTA)1Mmay Tg(tetO-Gnas)1593Mpke
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tg(Camk2a-tTA)1Mmay mutation (6 available)
Tg(tetO-Gnas)1593Mpke mutation (0 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
nervous system
• in mice never fed doxycycline or fed doxycycline only during development or only during adulthood (J:166114)
• in mice never fed doxycycline or fed doxycycline only during development or only during adulthood (J:166114)
• mice never fed doxycycline or fed doxycycline only during development or only during adulthood exhibit a decrease in dorsal striatum compared with wild-type mice (J:166114)
• mice never fed doxycycline or fed doxycycline only during development or only during adulthood exhibit a decrease in dorsal striatum compared with wild-type mice (J:166114)
• mice never fed doxycycline or fed doxycycline only during development or only during adulthood exhibit a decrease in ventral striatum compared with wild-type mice (J:166114)
• mice never fed doxycycline or fed doxycycline only during development or only during adulthood exhibit a decrease in ventral striatum compared with wild-type mice (J:166114)
• in mice never fed doxycycline but not mice fed doxycycline during adulthood only (J:166114)
• in mice never fed doxycycline but not mice fed doxycycline during adulthood only (J:166114)
• mice that never received doxycycline exhibit decreased prepulse inhibition compared with wild-type mice (J:166114)
• however, mice that receive doxycycline throughout development or only in adulthood or are treated with haloperidol exhibit normal prepulse inhibition (J:166114)
• mice that never received doxycycline exhibit decreased prepulse inhibition compared with wild-type mice (J:166114)
• however, mice that receive doxycycline throughout development or only in adulthood or are treated with haloperidol exhibit normal prepulse inhibition (J:166114)
• in mice never fed doxycycline but not mice fed doxycycline during adulthood only (J:166114)
• in mice never fed doxycycline but not mice fed doxycycline during adulthood only (J:166114)

behavior/neurological
N
• mice exhibit no change in anxiety-related behavior (J:166114)
• mice exhibit no change in anxiety-related behavior (J:166114)
• mice never fed doxycycline exhibit impaired short-term and long-term memory for hippocampus-dependent contextual fear compared with wild-type mice (J:166114)
• mice fed doxycycline only during adulthood or only during the retrieval but not training exhibit reduced levels of contextual fear 24 hours following training compared with wild-type mice (J:166114)
• however, mice fed doxycycline only during development or only after training through retrieval exhibit normal long-term memory for contextual fear (J:166114)
• mice never fed doxycycline exhibit impaired short-term and long-term memory for hippocampus-dependent contextual fear compared with wild-type mice (J:166114)
• mice fed doxycycline only during adulthood or only during the retrieval but not training exhibit reduced levels of contextual fear 24 hours following training compared with wild-type mice (J:166114)
• however, mice fed doxycycline only during development or only after training through retrieval exhibit normal long-term memory for contextual fear (J:166114)
• mice never fed doxycycline or only fed doxycycline during development but not during adulthood only exhibit impaired spatial learning in a Morris water maze compared with wild-type mice (J:166114)
• mice never fed doxycycline or only fed doxycycline during development but not during adulthood only exhibit impaired spatial learning in a Morris water maze compared with wild-type mice (J:166114)
• mice never fed doxycycline or only fed doxycycline during development or during adulthood only exhibit impaired spatial memory in a Morris water maze compared with wild-type mice (J:166114)
• mice never fed doxycycline or only fed doxycycline during development or during adulthood only exhibit impaired spatial memory in a Morris water maze compared with wild-type mice (J:166114)
• in mice never fed doxycycline or only fed doxycycline during adulthood but not during development only (J:166114)
• in mice never fed doxycycline or only fed doxycycline during adulthood but not during development only (J:166114)

Mouse Models of Human Disease
OMIM ID Ref(s)
Schizophrenia; SCZD 181500 J:166114




Genotype
MGI:5478560
cx8
Allelic
Composition
Tg(Camk2a-tTA)1Mmay/0
Tg(tetO-APPSwInd)107Dbo/0
Genetic
Background
(FVB/NJ x B6.Cg-Tg(tetO-APPSwInd)107Dbo Tg(Camk2a-tTA)1Mmay)F1
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tg(Camk2a-tTA)1Mmay mutation (6 available)
Tg(tetO-APPSwInd)107Dbo mutation (0 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
behavior/neurological
N
• bitransgenic (off-DOX) males perform like wild-type males in Plus water maze apparatus, swimming abilities, and latency to find platform (J:195259)
• bitransgenic (off-DOX) males perform like wild-type males in Plus water maze apparatus, swimming abilities, and latency to find platform (J:195259)
• in a test of long-term reference memory, radial arm water maze (RAWM) administered after a 24 hour delay, bi-transgenic males (off-DOX) performed at the level of chance with a significantly increased number of errors compared to wild type (J:195259)
• bi-transgenic mice (on-DOX) perform similar to non-transgenic controls in RAWM (J:195259)
• in a test of cognitive flexibility, as assessed by changing the water maze escape platform position daily, bi-transgenic males (on-DOX) continue to visit the original location significantly more frequently than non-transgenic controls, however, in subsequent sessions the error rate becomes similar to non-transgenic controls (J:195259)
• in a test of long-term reference memory, radial arm water maze (RAWM) administered after a 24 hour delay, bi-transgenic males (off-DOX) performed at the level of chance with a significantly increased number of errors compared to wild type (J:195259)
• bi-transgenic mice (on-DOX) perform similar to non-transgenic controls in RAWM (J:195259)
• in a test of cognitive flexibility, as assessed by changing the water maze escape platform position daily, bi-transgenic males (on-DOX) continue to visit the original location significantly more frequently than non-transgenic controls, however, in subsequent sessions the error rate becomes similar to non-transgenic controls (J:195259)
• 12.5 month old bi-transgenic males (off-DOX) exhibit significantly less preference for exploring the new arm of the two trial Y maze (a test of short term spatial memory) (J:195259)
• 12.5 month old bi-transgenic males (on-DOX) exhibit a preference for the new arm (J:195259)
• 12.5 month old bi-transgenic males (off-DOX) exhibit improved performance after successive trials, but an increased number of errors compared to wild-type non-Tg and on-DOX Tg controls in the radial arm water maze (RAWM), a test of long term spatial memory (J:195259)
• 12.5 month old bi-transgenic males (off-DOX) exhibit significantly less preference for exploring the new arm of the two trial Y maze (a test of short term spatial memory) (J:195259)
• 12.5 month old bi-transgenic males (on-DOX) exhibit a preference for the new arm (J:195259)
• 12.5 month old bi-transgenic males (off-DOX) exhibit improved performance after successive trials, but an increased number of errors compared to wild-type non-Tg and on-DOX Tg controls in the radial arm water maze (RAWM), a test of long term spatial memory (J:195259)

nervous system
• found in the CA layer of the hippocampus in off-DOX and on-DOX (for 7 days) 23 month old bi-transgenic males, however, after 5 weeks on doxycycline APP/amyloid beta (as assessed by mAb 6E10) immunoreactivity disappears (J:195259)
• a low level of mobile, water-extractable Abeta42 is present in bitransgenic males treated with DOX for up to 4 weeks (J:195259)
• found in the CA layer of the hippocampus in off-DOX and on-DOX (for 7 days) 23 month old bi-transgenic males, however, after 5 weeks on doxycycline APP/amyloid beta (as assessed by mAb 6E10) immunoreactivity disappears (J:195259)
• a low level of mobile, water-extractable Abeta42 is present in bitransgenic males treated with DOX for up to 4 weeks (J:195259)

homeostasis/metabolism
• found in the CA layer of the hippocampus in off-DOX and on-DOX (for 7 days) 23 month old bi-transgenic males, however, after 5 weeks on doxycycline APP/amyloid beta (as assessed by mAb 6E10) immunoreactivity disappears (J:195259)
• a low level of mobile, water-extractable Abeta42 is present in bitransgenic males treated with DOX for up to 4 weeks (J:195259)
• found in the CA layer of the hippocampus in off-DOX and on-DOX (for 7 days) 23 month old bi-transgenic males, however, after 5 weeks on doxycycline APP/amyloid beta (as assessed by mAb 6E10) immunoreactivity disappears (J:195259)
• a low level of mobile, water-extractable Abeta42 is present in bitransgenic males treated with DOX for up to 4 weeks (J:195259)




Genotype
MGI:5634918
cx9
Allelic
Composition
Bace1tm1Pcw/Bace1+
Tg(Camk2a-tTA)1Mmay/0
Tg(tetO-CDK5R1/GFP)337Lht/0
Genetic
Background
involves: 129S1/Sv * 129X1/SvJ * C57BL/6J
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Bace1tm1Pcw mutation (1 available); any Bace1 mutation (4 available)
Tg(Camk2a-tTA)1Mmay mutation (6 available)
Tg(tetO-CDK5R1/GFP)337Lht mutation (1 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
nervous system
N
• mice with transgene expression induced by removal of doxycycline from the food 4-6 weeks postnatal exhibit decreased amyloid beta in the hippocampus (J:177847)
• mice exhibit normal synaptic plasticity and long term potentiation (LTP) is fully restored following a 6-week induction (J:177847)
• mice exhibit normal density of synaptophysin puncta in the stratum radiatum of the hippocampus, indicating restoration of synapse density, following a 6-week induction (J:177847)
• mice with transgene expression induced by removal of doxycycline from the food 4-6 weeks postnatal exhibit decreased amyloid beta in the hippocampus (J:177847)
• mice exhibit normal synaptic plasticity and long term potentiation (LTP) is fully restored following a 6-week induction (J:177847)
• mice exhibit normal density of synaptophysin puncta in the stratum radiatum of the hippocampus, indicating restoration of synapse density, following a 6-week induction (J:177847)
• brain weight is reduced in 6-week induced mice (J:177847)
• brain weight is reduced in 6-week induced mice (J:177847)
• reduction in the number of NeuN-positive cells in hippocampal area CA1 in 6-week induced mice (J:177847)
• reduction in the number of NeuN-positive cells in hippocampal area CA1 in 6-week induced mice (J:177847)
• reactive astrogliosis is seen in the cortex and hippocampus in 6-week induced mice (J:177847)
• reactive astrogliosis is seen in the cortex and hippocampus in 6-week induced mice (J:177847)

behavior/neurological
N
• 6-week induced mice show improved associate learning in contextual fear conditioning and are indistinguishable from controls (J:177847)
• 6-week induced mice show improved associate learning in contextual fear conditioning and are indistinguishable from controls (J:177847)




Genotype
MGI:5693761
cx10
Allelic
Composition
Tg(Camk2a-tTA)1Mmay/?
Tg(tetO-DRD2)2-5Kndl/?
Genetic
Background
involves: 129S6/SvEvTac * C57BL/6 * CBA
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tg(Camk2a-tTA)1Mmay mutation (6 available)
Tg(tetO-DRD2)2-5Kndl mutation (1 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
behavior/neurological
• mice exhibit a behavioral flexibility deficit in bowl reversal test (J:106982)
• mice exhibit increased latency to choose between two odors in single discrimination reversal trials (J:106982)
• mice exhibit a behavioral flexibility deficit in bowl reversal test (J:106982)
• mice exhibit increased latency to choose between two odors in single discrimination reversal trials (J:106982)
• memory impairment is observed in the eight-arm radial win-shift delayed non-match to sample (DNMTS) maze (J:106982)
• impaired acquisition of task is observed in the DNMTS T-maze; controls reach preset criterion more quickly than transgenic mice (J:106982)
• performance deficit in the T maze exists in the presence or absence of doxycycline (J:106982)
• memory impairment is observed in the eight-arm radial win-shift delayed non-match to sample (DNMTS) maze (J:106982)
• impaired acquisition of task is observed in the DNMTS T-maze; controls reach preset criterion more quickly than transgenic mice (J:106982)
• performance deficit in the T maze exists in the presence or absence of doxycycline (J:106982)

homeostasis/metabolism
• increase in dopamine levels (J:106982)
• decrease in dopamine turnover as determined by DOPAC:DA and HVA:DA ratios (J:106982)
• increase in dopamine levels (J:106982)
• decrease in dopamine turnover as determined by DOPAC:DA and HVA:DA ratios (J:106982)
• decrease in basal metabolic activity in the caudate putamen as measured by glucose uptake (J:106982)
• increase in activity in primary motor and somatosensory cortices (J:106982)
• decrease in basal metabolic activity in the caudate putamen as measured by glucose uptake (J:106982)
• increase in activity in primary motor and somatosensory cortices (J:106982)

nervous system
• increase in dopamine levels (J:106982)
• decrease in dopamine turnover as determined by DOPAC:DA and HVA:DA ratios (J:106982)
• increase in dopamine levels (J:106982)
• decrease in dopamine turnover as determined by DOPAC:DA and HVA:DA ratios (J:106982)




Genotype
MGI:5694075
cx11
Allelic
Composition
Tg(Camk2a-tTA)1Mmay/0
Tg(tetO-Comt)1Kndl/0
Genetic
Background
involves: 129S6/SvEvTac * C57BL/6J
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tg(Camk2a-tTA)1Mmay mutation (6 available)
Tg(tetO-Comt)1Kndl mutation (1 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
behavior/neurological
• mice exhibit an increased number of continued (perseverative) responses to stimulus in the 5-Choice Serial Reaction Time Task, a measure of compulsive behavior (J:225566)
• mice exhibit an increased number of continued (perseverative) responses to stimulus in the 5-Choice Serial Reaction Time Task, a measure of compulsive behavior (J:225566)
• mice exhibit an increased number of premature responses prior to stimulus in the 5-Choice Serial Reaction Time Task, a measure of impulsive behavior (J:225566)
• mice exhibit an increased number of premature responses prior to stimulus in the 5-Choice Serial Reaction Time Task, a measure of impulsive behavior (J:225566)
• slower learning in stimulus-response (conditional associative learning-CAL), although mice attain same performance level after training (J:225566)
• mice exhibit slower learning to reach training criterion in assay for selective attention (5-Choice Serial Reaction Time Task - 5CSRTT), however once training is complete mice perform as well as controls (J:225566)
• slower learning in stimulus-response (conditional associative learning-CAL), although mice attain same performance level after training (J:225566)
• mice exhibit slower learning to reach training criterion in assay for selective attention (5-Choice Serial Reaction Time Task - 5CSRTT), however once training is complete mice perform as well as controls (J:225566)
• mice exhibit a deficit in nonspatial working memory in test of increasing delay length between offset of auditory cue and availability of response lever (J:225566)
• mice exhibit a deficit in nonspatial working memory in test of increasing delay length between offset of auditory cue and availability of response lever (J:225566)

nervous system
• increase in dopamine release capacity in the dorsomedial striatum following stimulation of the medial forebrain bundle in comparison to controls (J:225566)
• higher average peak dopamine current (J:225566)
• increased total release volume (J:225566)
• increase in dopamine release capacity in the dorsomedial striatum following stimulation of the medial forebrain bundle in comparison to controls (J:225566)
• higher average peak dopamine current (J:225566)
• increased total release volume (J:225566)




Genotype
MGI:5558945
cx12
Allelic
Composition
Tg(Camk2a-tTA)1Mmay/0
Tg(tetO-MAPT*P301L)#Kha/0
Genetic
Background
involves: 129S6/SvEvTac * FVB/N
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tg(Camk2a-tTA)1Mmay mutation (6 available)
Tg(tetO-MAPT*P301L)#Kha mutation (2 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
behavior/neurological
• amount of time spent in open arms of elevated plus maze is increased relative to nontransgenic mice at 6 and 10 months of age, but not 2 months (J:207366)
• higher ratio of time spent in open not closed arms relative to nontransgenic mice at 10 months of age, but not 2 or 6 months (J:207366)
• exploration of light chamber is increased relative to nontransgenic mice at 6 months of age, but not 2 or 10 months (J:207366)
• higher ratio of time spent in light not dark relative to nontransgenic miceat 10 months of age, but not 2 or 6 months (J:207366)
• amount of time spent in open arms of elevated plus maze is increased relative to nontransgenic mice at 6 and 10 months of age, but not 2 months (J:207366)
• higher ratio of time spent in open not closed arms relative to nontransgenic mice at 10 months of age, but not 2 or 6 months (J:207366)
• exploration of light chamber is increased relative to nontransgenic mice at 6 months of age, but not 2 or 10 months (J:207366)
• higher ratio of time spent in light not dark relative to nontransgenic miceat 10 months of age, but not 2 or 6 months (J:207366)
• decreased tendency to explore the center of the open field relative to nontransgenic mice (J:207366)
• decreased tendency to explore the center of the open field relative to nontransgenic mice (J:207366)
• progressive decrease in percent of time spent freezing in response to unconditioned stimulus beginning at 2 months of age (J:207366)
• progressive decrease in percent of time spent freezing in response to unconditioned stimulus beginning at 2 months of age (J:207366)
• progressive decrease in percent of time spent freezing in response to conditioned stimulus beginning at 6 months of age (J:207366)
• progressive decrease in percent of time spent freezing in response to conditioned stimulus beginning at 6 months of age (J:207366)
• mice exhibit progressive hyperactivity in open field analysis and elevated plus maze (J:207366)
• total distance travelled in open field assay is increased relative to nontransgenic mice at 6 and 10 months of age, but not 2 months (J:207366)
• average speed is increased relative to nontransgenic mice at 6 and 10 months of age, but not 2 months (J:207366)
• total time spent immobile is increased relative to nontransgenic mice at 6 and 10 months of age, but not 2 months (J:207366)
• mice exhibit progressive hyperactivity in open field analysis and elevated plus maze (J:207366)
• total distance travelled in open field assay is increased relative to nontransgenic mice at 6 and 10 months of age, but not 2 months (J:207366)
• average speed is increased relative to nontransgenic mice at 6 and 10 months of age, but not 2 months (J:207366)
• total time spent immobile is increased relative to nontransgenic mice at 6 and 10 months of age, but not 2 months (J:207366)

nervous system
• neurofibrilliary tangles are observed by immunostaining in the CA1 region of the hippocampus beginning at 6 months of age and progressing to an extensive pathology by 11 months of age (J:207366)
• neurofibrilliary tangles are observed by immunostaining in the amygdala beginning at 2 months of age and progressing to an extensive pathology by 10 months of age (J:207366)
• neurofibrilliary tangles are observed by immunostaining in the CA1 region of the hippocampus beginning at 6 months of age and progressing to an extensive pathology by 11 months of age (J:207366)
• neurofibrilliary tangles are observed by immunostaining in the amygdala beginning at 2 months of age and progressing to an extensive pathology by 10 months of age (J:207366)
• tau burden increases with age in the amygdala and CA1 region of the hippocampus (J:207366)
• tau burden increases with age in the amygdala and CA1 region of the hippocampus (J:207366)

Mouse Models of Human Disease
OMIM ID Ref(s)
Frontotemporal Dementia; FTD 600274 J:207366




Genotype
MGI:4819951
cx13
Allelic
Composition
Tg(Camk2a-tTA)1Mmay/?
Tg(tetO-MAPT*P301L)#Kha/?
Genetic
Background
involves: 129S6/SvEvTac * FVB/N
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tg(Camk2a-tTA)1Mmay mutation (6 available)
Tg(tetO-MAPT*P301L)#Kha mutation (2 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
nervous system
• a significant loss in brain weight by 5.5 months (J:99626)
• when treated with doxycycline during 5.5 to 10 months, the loss of brain weight was significantly protected (J:99626)
• a significant loss in brain weight by 5.5 months (J:99626)
• when treated with doxycycline during 5.5 to 10 months, the loss of brain weight was significantly protected (J:99626)
• significant decrease in total numbers of CA1 hippocampal neurons (J:99626)
• CA1 neuron estimates were stabilized after brief (6- to 8-week) doxycycline treatment (J:99626)
• significant decrease in total numbers of CA1 hippocampal neurons (J:99626)
• CA1 neuron estimates were stabilized after brief (6- to 8-week) doxycycline treatment (J:99626)
• gross atrophy of the forebrain was evident in a 10-month-old mouse (J:99626)
• gross atrophy of the forebrain was evident in a 10-month-old mouse (J:99626)
• develop argyrophilic tangle-like inclusions in the cortex by 4 months and in the hippocampal formation by 5.5 months (J:99626)
• when treated with doxycycline at 2.5 month, the tau pathology ceased to progress (J:99626)
• develop argyrophilic tangle-like inclusions in the cortex by 4 months and in the hippocampal formation by 5.5 months (J:99626)
• when treated with doxycycline at 2.5 month, the tau pathology ceased to progress (J:99626)
• the neuronal inclusions composed of a mass of straight tau filaments (J:99626)
• when treated with doxycycline at 2.5 month, the tau pathology ceased to progress (J:99626)
• the neuronal inclusions composed of a mass of straight tau filaments (J:99626)
• when treated with doxycycline at 2.5 month, the tau pathology ceased to progress (J:99626)
• approximately 23% of CA1 pyramidal cells remaining at 8.5 months (J:99626)
• CA1 neuron estimates were stabilized after brief (6- to 8-week) doxycycline treatment (J:99626)
• approximately 23% of CA1 pyramidal cells remaining at 8.5 months (J:99626)
• CA1 neuron estimates were stabilized after brief (6- to 8-week) doxycycline treatment (J:99626)

behavior/neurological
• he retention of spatial memory examined by the Morris water maze were impaired as the mice aged (J:99626)
• deficit in spatial navigation was also seen in younger mice (J:99626)
• the performance improved when treated with doxycycline at 2.5 month-old or at 5.5 month-old (J:99626)
• he retention of spatial memory examined by the Morris water maze were impaired as the mice aged (J:99626)
• deficit in spatial navigation was also seen in younger mice (J:99626)
• the performance improved when treated with doxycycline at 2.5 month-old or at 5.5 month-old (J:99626)

Mouse Models of Human Disease
OMIM ID Ref(s)
Alzheimer Disease; AD 104300 J:99626




Genotype
MGI:4452245
cx14
Allelic
Composition
Tg(Camk2a-tTA)1Mmay/0
Tg(tetO-Csnk1d)#Mfla/0
Genetic
Background
involves: 129/Sv * C57BL/6
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tg(Camk2a-tTA)1Mmay mutation (6 available)
Tg(tetO-Csnk1d)#Mfla mutation (0 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
behavior/neurological
N
• mice exhibit normal social and circadian behaviors (J:158611)
• mice exhibit normal social and circadian behaviors (J:158611)
• mice exhibit a 40 minute delay in D-amphetamine-induced hyperlocomotion compared with similarly treated wild-type mice (J:158611)
• D-amphetamine-treated mice exhibit a dose dependent suppression of vertical activity unlike similarly treated wild-type mice that exhibit an increase in vertical activity (J:158611)
• mice exhibit a 40 minute delay in D-amphetamine-induced hyperlocomotion compared with similarly treated wild-type mice (J:158611)
• D-amphetamine-treated mice exhibit a dose dependent suppression of vertical activity unlike similarly treated wild-type mice that exhibit an increase in vertical activity (J:158611)
• in a dark-light choice test, mice exhibit increased rearing in the light compartment compared with wild-type mice (J:158611)
• in an elevated place maze, mice spend more time in the open arms than wild-type mice (J:158611)
• in a novelty suppressed feeding paradigm, mice exhibit shorter latency to feeding compared with wild-type mice (J:158611)
• however, mice exhibit normal anxiety-related behavior in an open field, forced swim, and tail suspension tests (J:158611)
• in a dark-light choice test, mice exhibit increased rearing in the light compartment compared with wild-type mice (J:158611)
• in an elevated place maze, mice spend more time in the open arms than wild-type mice (J:158611)
• in a novelty suppressed feeding paradigm, mice exhibit shorter latency to feeding compared with wild-type mice (J:158611)
• however, mice exhibit normal anxiety-related behavior in an open field, forced swim, and tail suspension tests (J:158611)
• mice exhibit a 40 minute delay in D-amphetamine-induced hyperlocomotion compared with similarly treated wild-type mice (J:158611)
• D-amphetamine-treated mice exhibit a dose dependent suppression of vertical activity unlike similarly treated wild-type mice that exhibit an increase in vertical activity (J:158611)
• mice exhibit a 40 minute delay in D-amphetamine-induced hyperlocomotion compared with similarly treated wild-type mice (J:158611)
• D-amphetamine-treated mice exhibit a dose dependent suppression of vertical activity unlike similarly treated wild-type mice that exhibit an increase in vertical activity (J:158611)
• in an open field test, mice exhibit increased vertical activity compared with wild-type mice (J:158611)
• increased activity begins at 6 weeks of age and persists at least until 16 months of age (J:158611)
• however, treatment with methylphenidate or haloperidol suppresses vertical activity (J:158611)
• in an open field test, mice exhibit increased vertical activity compared with wild-type mice (J:158611)
• increased activity begins at 6 weeks of age and persists at least until 16 months of age (J:158611)
• however, treatment with methylphenidate or haloperidol suppresses vertical activity (J:158611)
• in an open field test, mice exhibit increased horizontal and vertical activity compared with wild-type mice (J:158611)
• increased activity begins at 6 weeks of age and persists at least until 16 months of age (J:158611)
• however, treatment with methylphenidate or haloperidol decreases activity levels (J:158611)
• in an open field test, mice exhibit increased horizontal and vertical activity compared with wild-type mice (J:158611)
• increased activity begins at 6 weeks of age and persists at least until 16 months of age (J:158611)
• however, treatment with methylphenidate or haloperidol decreases activity levels (J:158611)
• in an open field box, mice fail to build a nest unlike wild-type mice (J:158611)
• in an open field box, mice fail to build a nest unlike wild-type mice (J:158611)

nervous system
• protein expression of dopamine receptors 1 and 2 and NMDA receptors are decreased in the striatum compared to in wild-type mice (J:158611)
• protein expression of dopamine receptors 1 and 2 and NMDA receptors are decreased in the striatum compared to in wild-type mice (J:158611)

homeostasis/metabolism
• MK801-treated mice exhibit a more rapid onset of increased horizontal activity and decreased vertical activity compared with similarly treated wild-type mice (J:158611)
• MK801-treated mice exhibit a more rapid onset of increased horizontal activity and decreased vertical activity compared with similarly treated wild-type mice (J:158611)

Mouse Models of Human Disease
OMIM ID Ref(s)
Attention Deficit-Hyperactivity Disorder; ADHD 143465 J:158611




Genotype
MGI:5438795
cx15
Allelic
Composition
Tg(Camk2a-tTA)1Mmay/0
Tg(tetO-MAPT*P301L)#Kha/0
Genetic
Background
involves: 129/Sv * C57BL/6 * CBA * FVB/N
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tg(Camk2a-tTA)1Mmay mutation (6 available)
Tg(tetO-MAPT*P301L)#Kha mutation (2 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
nervous system
• progressive atrophy of dentate granule cells (J:185792)
• progressive atrophy of dentate granule cells (J:185792)
• progressive atrophy of hippocampal pyramidal neurons (J:185792)
• progressive atrophy of hippocampal pyramidal neurons (J:185792)




Genotype
MGI:4421006
cx16
Allelic
Composition
Lrrk2tm1.1Cai/Lrrk2+
Tg(Camk2a-tTA)1Mmay/0
Tg(tetO-SNCA*A53T)E2Cai/0
Genetic
Background
involves: 129X1/SvJ * C57BL/6
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Lrrk2tm1.1Cai mutation (1 available); any Lrrk2 mutation (15 available)
Tg(Camk2a-tTA)1Mmay mutation (6 available)
Tg(tetO-SNCA*A53T)E2Cai mutation (1 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
nervous system
• somatic alpha synuclein in neurons is apparent at 12 months (J:156512)
• somatic alpha synuclein in neurons is apparent at 12 months (J:156512)
• increased microglial activation is observed in the brain at 12 months (J:156512)
• increased microglial activation is observed in the brain at 12 months (J:156512)
• numbers of residual neurons is significantly lower than non transgenic controls (J:156512)
• numbers of residual neurons is significantly lower than non transgenic controls (J:156512)
• significant at 12 months (J:156512)
• significant at 12 months (J:156512)
• the Golgi complex shows severe fragmentation in 12 month old animals (J:156512)
• the Golgi complex shows severe fragmentation in 12 month old animals (J:156512)
• neurodegeneration significant at 12 months (J:156512)
• neurodegeneration significant at 12 months (J:156512)

immune system
• increased microglial activation is observed in the brain at 12 months (J:156512)
• increased microglial activation is observed in the brain at 12 months (J:156512)

hematopoietic system
• increased microglial activation is observed in the brain at 12 months (J:156512)
• increased microglial activation is observed in the brain at 12 months (J:156512)




Genotype
MGI:4421016
cx17
Allelic
Composition
Lrrk2tm1.1Cai/Lrrk2tm1.1Cai
Tg(Camk2a-tTA)1Mmay/0
Tg(tetO-SNCA*A53T)E2Cai/0
Genetic
Background
involves: 129X1/SvJ * C57BL/6
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Lrrk2tm1.1Cai mutation (1 available); any Lrrk2 mutation (15 available)
Tg(Camk2a-tTA)1Mmay mutation (6 available)
Tg(tetO-SNCA*A53T)E2Cai mutation (1 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
nervous system
N
• no apparent neurodegeneration is observed in 12-month old mice; no significant elevation of astrocytosis, microgliosis or somatic accumulation of alpha-synuclein is detected in striatum at 12 months (J:156512)
• no apparent neurodegeneration is observed in 12-month old mice; no significant elevation of astrocytosis, microgliosis or somatic accumulation of alpha-synuclein is detected in striatum at 12 months (J:156512)




Genotype
MGI:5289971
cx18
Allelic
Composition
Tg(Camk2a-tTA)1Mmay/0
Tg(tetO-SNCA*A53T)33Vle/0
Genetic
Background
involves: C3H/HeH * C57BL/6
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tg(Camk2a-tTA)1Mmay mutation (6 available)
Tg(tetO-SNCA*A53T)33Vle mutation (1 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
nervous system
• dentate gyrus neuron loss is due to cell death not decreased cell proliferation (J:156801)
• dentate gyrus neuron loss is due to cell death not decreased cell proliferation (J:156801)
• mild hippocampal dentate gyrus neuron atrophy is seen at P14, and is striking by P21 (J:156801)
• mice treated with doxycycline to suppress alpha-synuclein expression, do not exhibit neuron atrophy (J:156801)
• mild hippocampal dentate gyrus neuron atrophy is seen at P14, and is striking by P21 (J:156801)
• mice treated with doxycycline to suppress alpha-synuclein expression, do not exhibit neuron atrophy (J:156801)
• mutants fed a doxycycline diet to suppress transgene expression from E0.5 until P21 and then switched to a regular diet to induce transgene expression exhibit severe loss of dentate gyrus granule cells (J:174555)
• mutants fed a doxycycline diet to suppress transgene expression from E0.5 until P21 and then switched to a regular diet to induce transgene expression exhibit severe loss of dentate gyrus granule cells (J:174555)
• mutants fed a doxycycline diet to suppress transgene expression from E0.5 until P21 and then switched to a regular diet to induce transgene expression exhibit severe loss of hippocampal pyramidal cells (J:174555)
• mutants fed a doxycycline diet to suppress transgene expression from E0.5 until P21 and then switched to a regular diet to induce transgene expression exhibit severe loss of hippocampal pyramidal cells (J:174555)
• mutants fed a doxycycline diet to suppress transgene expression from E0.5 until P21 and then switched to a regular diet to induce transgene expression exhibit severe reduction in cortex thickness (J:174555)
• mutants fed a doxycycline diet to suppress transgene expression from E0.5 until P21 and then switched to a regular diet to induce transgene expression exhibit severe reduction in cortex thickness (J:174555)
• gliosis in the hippocampus, near the dentate gyrus (J:156801)
• gliosis in the hippocampus, near the dentate gyrus (J:156801)
• mutants fed a doxycycline diet to suppress transgene expression from E0.5 until P21 and then switched to a regular diet to induce transgene expression exhibit progressive reactive astrogliosis; mutants further treated with doxycycline at 9 months, show prevention of further reactive gliosis (J:174555)
• mutants fed a doxycycline diet to suppress transgene expression from E0.5 until P21 and then switched to a regular diet to induce transgene expression exhibit progressive reactive astrogliosis; mutants further treated with doxycycline at 9 months, show prevention of further reactive gliosis (J:174555)
• mutants fed a doxycycline diet to suppress transgene expression from E0.5 until P21 and then switched to a regular diet to induce transgene expression exhibit a reduction in presynaptic vesicle proteins indicating a disruption in synaptic vesicles in the mossy fiber terminals (J:174555)
• mutants fed a doxycycline diet to suppress transgene expression from E0.5 until P21 and then switched to a regular diet to induce transgene expression exhibit a reduction in presynaptic vesicle proteins indicating a disruption in synaptic vesicles in the mossy fiber terminals (J:174555)
• mutants fed a doxycycline diet to suppress transgene expression from E0.5 until P21 and then switched to a regular diet to induce expression exhibit abnormal accumulation of alpha-synuclein in limbic areas including the cingulated cortex, the hippocampus, dentate gyrus, and mammillary body, as well as the olfactory bulb, septum and subthalamic nucleus, by 4 months of age; superior colliculus, ventral tegmental area, brainstem, and spinal cord also shows a limited amount of alpha-synuclein accumulation (J:174555)
• young mice (4-12 months) fed a doxycycline diet to suppress transgene expression from E0.5 until P21 and then switched to a regular diet to induce expression exhibit early, soluble, neuritic, and synaptic accumulations, which over time progress to become insoluble cytoplasmic inclusions at 20 months (J:174555)
• mice treated with doxycyline starting at 9 months for 3 months and analyzed at 12 months do not exhibit abnormal alpha-synuclein accumulations in the hippocampus or dentate gyrus; doxycycline however did not clear alpha-synuclein pathology in the mammillary bodies, olfactory bulb or septum, but did arrest further accumulation progression (J:174555)
• mutants fed a doxycycline diet to suppress transgene expression from E0.5 until P21 and then switched to a regular diet to induce expression exhibit abnormal accumulation of alpha-synuclein in limbic areas including the cingulated cortex, the hippocampus, dentate gyrus, and mammillary body, as well as the olfactory bulb, septum and subthalamic nucleus, by 4 months of age; superior colliculus, ventral tegmental area, brainstem, and spinal cord also shows a limited amount of alpha-synuclein accumulation (J:174555)
• young mice (4-12 months) fed a doxycycline diet to suppress transgene expression from E0.5 until P21 and then switched to a regular diet to induce expression exhibit early, soluble, neuritic, and synaptic accumulations, which over time progress to become insoluble cytoplasmic inclusions at 20 months (J:174555)
• mice treated with doxycyline starting at 9 months for 3 months and analyzed at 12 months do not exhibit abnormal alpha-synuclein accumulations in the hippocampus or dentate gyrus; doxycycline however did not clear alpha-synuclein pathology in the mammillary bodies, olfactory bulb or septum, but did arrest further accumulation progression (J:174555)
• neuronal loss in the cortex and hippocampus is seen in 20-22 old mutants fed a doxycycline diet to suppress transgene expression from E0.5 until P21 and then switched to a regular diet to induce transgene expression (J:174555)
• neuronal loss in the cortex and hippocampus is seen in 20-22 old mutants fed a doxycycline diet to suppress transgene expression from E0.5 until P21 and then switched to a regular diet to induce transgene expression (J:174555)
• postmitotic hippocampal dentate gyrus neuron degeneration is seen by P14, but no degeneration of proliferating cells (J:156801)
• postmitotic hippocampal dentate gyrus neuron degeneration is seen by P14, but no degeneration of proliferating cells (J:156801)

behavior/neurological
• mutants fed a doxycycline diet to suppress transgene expression from E0.5 until P21 and then switched to a regular diet to induce transgene expression exhibit impaired contextual fear memory at 8 months of age; mutants further treated with doxycycline at 9 months show improved memory function (J:174555)
• normal chow-fed mutants at 12 months of age show impaired contextual fear memory (J:174555)
• mutants fed a doxycycline diet to suppress transgene expression from E0.5 until P21 and then switched to a regular diet to induce transgene expression exhibit impaired contextual fear memory at 8 months of age; mutants further treated with doxycycline at 9 months show improved memory function (J:174555)
• normal chow-fed mutants at 12 months of age show impaired contextual fear memory (J:174555)

cellular
• dentate gyrus neuron loss is due to cell death not decreased cell proliferation (J:156801)
• dentate gyrus neuron loss is due to cell death not decreased cell proliferation (J:156801)

Mouse Models of Human Disease
OMIM ID Ref(s)
Dementia, Lewy Body; DLB 127750 J:174555




Genotype
MGI:5289970
cx19
Allelic
Composition
Tg(Camk2a-tTA)1Mmay/0
Tg(tetO-SNCA)7Vle/0
Genetic
Background
involves: C3H/HeH * C57BL/6
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tg(Camk2a-tTA)1Mmay mutation (6 available)
Tg(tetO-SNCA)7Vle mutation (0 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
nervous system
• atrophy of hippocampal dentate gyrus neurons is seen by P21 (J:156801)
• atrophy of hippocampal dentate gyrus neurons is seen by P21 (J:156801)
• mutants fed a doxycycline diet to suppress transgene expression from E0.5 until P21 and then switched to a regular diet to induce expression show accumulation of alpha-synuclein within neurons of the septum, cingulated cortex, subthalamic nucleus, mammillary body, and brainstem, but not hippocampus at 8 months of age (J:174555)
• mutants fed a doxycycline diet to suppress transgene expression from E0.5 until P21 and then switched to a regular diet to induce expression show accumulation of alpha-synuclein within neurons of the septum, cingulated cortex, subthalamic nucleus, mammillary body, and brainstem, but not hippocampus at 8 months of age (J:174555)

behavior/neurological
N
• mutants do not exhibit impaired contextual fear memory at 8 months of age (J:174555)
• mutants do not exhibit impaired contextual fear memory at 8 months of age (J:174555)




Genotype
MGI:4421004
cx20
Allelic
Composition
Tg(Camk2a-tTA)1Mmay/0
Tg(tetO-APPSwInd)885Dbo/0
Tg(tetO-LRRK2*G2019S)E3Cai/0
Genetic
Background
involves: C3H/HeJ * C57BL/6
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tg(Camk2a-tTA)1Mmay mutation (6 available)
Tg(tetO-APPSwInd)885Dbo mutation (0 available)
Tg(tetO-LRRK2*G2019S)E3Cai mutation (1 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
nervous system
• no acceleration of degeneration is observed compared to Tg(Camk2a-tTA)1Mmay/Tg(tetO-LRRK2*G2019S)E3Cai mice (G2019S) (J:156512)
• no acceleration of degeneration is observed compared to Tg(Camk2a-tTA)1Mmay/Tg(tetO-LRRK2*G2019S)E3Cai mice (G2019S) (J:156512)




Genotype
MGI:3709152
cx21
Allelic
Composition
Tg(Camk2a-tTA)1Mmay/0
Tg(tetO-APPSwInd)107Dbo/0
Genetic
Background
involves: C3H/HeJ * C57BL/6 * CBA
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tg(Camk2a-tTA)1Mmay mutation (6 available)
Tg(tetO-APPSwInd)107Dbo mutation (0 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
nervous system
• doxycycline-mediated suppression of transgenic APPSwInd synthesis leads to parallel reductions of amyloid beta peptide levels (J:109829)
• early onset amyloid formation is observed, with plaques observed as early as 8 weeks of age in mice receiving no doxycycline (DOX) treatment (J:109829)
• plaques are restricted to the forebrain, including the cortex, hippocampus, olfactory bulb, and striatum; by 6 months, amyloid burden covers large cortical and hippocampal areas (J:109829)
• first observed plaques are fibrillar-core deposits; in 6 month old animals, diffuse plaques are apparent and these are abundant at 9 months, while in 9-12 month-old mice, plaques are visible in the thalamus (J:109829)
• no lesions are observed in the cerebellum or brain stem (J:109829)
• animals receiving no treatment display moderate amyloid pathology at 6 months, which progresses to a severe amyloid burden by 9 months (J:109829)
• mice raised for 6 months with no (DOX) treatment, followed by 3 or 6 months of DOX treatment show similar pathology to untreated 6-month old animals, despite relatively long lesion clearance times (J:109829)
• doxycycline-mediated suppression of transgenic APPSwInd synthesis leads to parallel reductions of amyloid beta peptide levels (J:109829)
• early onset amyloid formation is observed, with plaques observed as early as 8 weeks of age in mice receiving no doxycycline (DOX) treatment (J:109829)
• plaques are restricted to the forebrain, including the cortex, hippocampus, olfactory bulb, and striatum; by 6 months, amyloid burden covers large cortical and hippocampal areas (J:109829)
• first observed plaques are fibrillar-core deposits; in 6 month old animals, diffuse plaques are apparent and these are abundant at 9 months, while in 9-12 month-old mice, plaques are visible in the thalamus (J:109829)
• no lesions are observed in the cerebellum or brain stem (J:109829)
• animals receiving no treatment display moderate amyloid pathology at 6 months, which progresses to a severe amyloid burden by 9 months (J:109829)
• mice raised for 6 months with no (DOX) treatment, followed by 3 or 6 months of DOX treatment show similar pathology to untreated 6-month old animals, despite relatively long lesion clearance times (J:109829)
• mice exhibit a progressive neuronal atrophy that is most pronounced in the granule cell layer of hippocampal dentate gyrus (J:185792)
• mice exhibit a progressive neuronal atrophy that is most pronounced in the granule cell layer of hippocampal dentate gyrus (J:185792)
• mice exhibit a progressive neuronal atrophy that is most pronounced in the granule cell layer of hippocampal dentate gyrus (J:185792)
• however, when mice are reared on doxycycline, cell loss is not observed (J:185792)
• mice exhibit a progressive neuronal atrophy that is most pronounced in the granule cell layer of hippocampal dentate gyrus (J:185792)
• however, when mice are reared on doxycycline, cell loss is not observed (J:185792)
• first visible plaques are fibrillary-cored deposits (J:109829)
• first visible plaques are fibrillary-cored deposits (J:109829)
• activated astrocytes are found near plaques in all affected mice glial pathology is more severe in older mice (J:109829)
• if transgene expression is suppressed with doxycycline treatment, pathology does not progress in severity (J:109829)
• activated astrocytes are found near plaques in all affected mice glial pathology is more severe in older mice (J:109829)
• if transgene expression is suppressed with doxycycline treatment, pathology does not progress in severity (J:109829)
• mice produce transgenic APP protein at 10- to 30-fold over endogenous App levels (J:109829)
• sensitivity of transgene suppression by doxycycline is intermediate between mice of line 885 and line 102 (J:109829)
• mice produce transgenic APP protein at 10- to 30-fold over endogenous App levels (J:109829)
• sensitivity of transgene suppression by doxycycline is intermediate between mice of line 885 and line 102 (J:109829)
• neuritic pathology is observed around plaques; neuritic pathology is more severe in older mice (J:109829)
• if transgene expression is suppressed with doxycycline treatment, pathology does not progress in severity (J:109829)
• neuritic pathology is observed around plaques; neuritic pathology is more severe in older mice (J:109829)
• if transgene expression is suppressed with doxycycline treatment, pathology does not progress in severity (J:109829)

behavior/neurological
• all animals raised with doxycycline have altered circadian rhythms with less distinction between day- and nighttime activity levels (J:109829)
• all animals raised with doxycycline have altered circadian rhythms with less distinction between day- and nighttime activity levels (J:109829)
• hyperactive behavior is partially reversed in some mice by 1 month of transgene suppression starting at 4-5 months of age (J:109829)
• hyperactive behavior is partially reversed in some mice by 1 month of transgene suppression starting at 4-5 months of age (J:109829)
• untreated mice show hyperactivity, often running in circles around the perimeter of cages (J:109829)
• similar patterns of activity are observed in Morris water maze, with repetitive swim patterns seen in radial water maze swim test (J:109829)
• hyperactive phenotype penetrance is ~100% (J:109829)
• untreated mice show 10-fold more ambulatory activity during the dark phase; even in light phase, activity is several-fold increased compared to wild-type controls; this activity is completely abolished in mice raised on doxycycline (J:109829)
• untreated mice show hyperactivity, often running in circles around the perimeter of cages (J:109829)
• similar patterns of activity are observed in Morris water maze, with repetitive swim patterns seen in radial water maze swim test (J:109829)
• hyperactive phenotype penetrance is ~100% (J:109829)
• untreated mice show 10-fold more ambulatory activity during the dark phase; even in light phase, activity is several-fold increased compared to wild-type controls; this activity is completely abolished in mice raised on doxycycline (J:109829)

immune system
• neuritic pathology is observed around plaques; neuritic pathology is more severe in older mice (J:109829)
• if transgene expression is suppressed with doxycycline treatment, pathology does not progress in severity (J:109829)
• neuritic pathology is observed around plaques; neuritic pathology is more severe in older mice (J:109829)
• if transgene expression is suppressed with doxycycline treatment, pathology does not progress in severity (J:109829)

homeostasis/metabolism
• doxycycline-mediated suppression of transgenic APPSwInd synthesis leads to parallel reductions of amyloid beta peptide levels (J:109829)
• early onset amyloid formation is observed, with plaques observed as early as 8 weeks of age in mice receiving no doxycycline (DOX) treatment (J:109829)
• plaques are restricted to the forebrain, including the cortex, hippocampus, olfactory bulb, and striatum; by 6 months, amyloid burden covers large cortical and hippocampal areas (J:109829)
• first observed plaques are fibrillar-core deposits; in 6 month old animals, diffuse plaques are apparent and these are abundant at 9 months, while in 9-12 month-old mice, plaques are visible in the thalamus (J:109829)
• no lesions are observed in the cerebellum or brain stem (J:109829)
• animals receiving no treatment display moderate amyloid pathology at 6 months, which progresses to a severe amyloid burden by 9 months (J:109829)
• mice raised for 6 months with no (DOX) treatment, followed by 3 or 6 months of DOX treatment show similar pathology to untreated 6-month old animals, despite relatively long lesion clearance times (J:109829)
• doxycycline-mediated suppression of transgenic APPSwInd synthesis leads to parallel reductions of amyloid beta peptide levels (J:109829)
• early onset amyloid formation is observed, with plaques observed as early as 8 weeks of age in mice receiving no doxycycline (DOX) treatment (J:109829)
• plaques are restricted to the forebrain, including the cortex, hippocampus, olfactory bulb, and striatum; by 6 months, amyloid burden covers large cortical and hippocampal areas (J:109829)
• first observed plaques are fibrillar-core deposits; in 6 month old animals, diffuse plaques are apparent and these are abundant at 9 months, while in 9-12 month-old mice, plaques are visible in the thalamus (J:109829)
• no lesions are observed in the cerebellum or brain stem (J:109829)
• animals receiving no treatment display moderate amyloid pathology at 6 months, which progresses to a severe amyloid burden by 9 months (J:109829)
• mice raised for 6 months with no (DOX) treatment, followed by 3 or 6 months of DOX treatment show similar pathology to untreated 6-month old animals, despite relatively long lesion clearance times (J:109829)

Mouse Models of Human Disease
OMIM ID Ref(s)
Alzheimer Disease; AD 104300 J:109829




Genotype
MGI:3709154
cx22
Allelic
Composition
Tg(Camk2a-tTA)1Mmay/0
Tg(tetO-APPSwInd)18Dbo/0
Genetic
Background
involves: C3H/HeJ * C57BL/6 * CBA
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tg(Camk2a-tTA)1Mmay mutation (6 available)
Tg(tetO-APPSwInd)18Dbo mutation (0 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
nervous system
• amyloid burden worsens in untreated animals between 6 and 9 months of age (J:109829)
• with 3 months of doxycyclin treatment beginning at 6 months of age, suppression of transgene synthesis and complete arrest of increase in amyloid pathology is observed compared to untreated mice; however, in these mice no sign of reduction in amyloid burden is observed (J:109829)
• amyloid burden worsens in untreated animals between 6 and 9 months of age (J:109829)
• with 3 months of doxycyclin treatment beginning at 6 months of age, suppression of transgene synthesis and complete arrest of increase in amyloid pathology is observed compared to untreated mice; however, in these mice no sign of reduction in amyloid burden is observed (J:109829)
• mice produce transgenic APP protein at 10- to 30-fold over endogenous App levels (J:109829)
• sensitivity of transgene suppression by doxycycline is intermediate between mice of line 885 and line 102 (J:109829)
• mice produce transgenic APP protein at 10- to 30-fold over endogenous App levels (J:109829)
• sensitivity of transgene suppression by doxycycline is intermediate between mice of line 885 and line 102 (J:109829)

homeostasis/metabolism
• amyloid burden worsens in untreated animals between 6 and 9 months of age (J:109829)
• with 3 months of doxycyclin treatment beginning at 6 months of age, suppression of transgene synthesis and complete arrest of increase in amyloid pathology is observed compared to untreated mice; however, in these mice no sign of reduction in amyloid burden is observed (J:109829)
• amyloid burden worsens in untreated animals between 6 and 9 months of age (J:109829)
• with 3 months of doxycyclin treatment beginning at 6 months of age, suppression of transgene synthesis and complete arrest of increase in amyloid pathology is observed compared to untreated mice; however, in these mice no sign of reduction in amyloid burden is observed (J:109829)

Mouse Models of Human Disease
OMIM ID Ref(s)
Alzheimer Disease; AD 104300 J:109829




Genotype
MGI:3709182
cx23
Allelic
Composition
Tg(Camk2a-tTA)1Mmay/0
Tg(tetO-APPSwInd)102Dbo/0
Genetic
Background
involves: C3H/HeJ * C57BL/6 * CBA
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tg(Camk2a-tTA)1Mmay mutation (6 available)
Tg(tetO-APPSwInd)102Dbo mutation (0 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
nervous system
• mice produce transgenic APP protein at 10- to 30-fold over endogenous App levels (J:109829)
• suppression of transgene expression in these mice is most sensitive to doxycycline of the four lines tested (J:109829)
• mice produce transgenic APP protein at 10- to 30-fold over endogenous App levels (J:109829)
• suppression of transgene expression in these mice is most sensitive to doxycycline of the four lines tested (J:109829)

Mouse Models of Human Disease
OMIM ID Ref(s)
Alzheimer Disease; AD 104300 J:109829




Genotype
MGI:3696400
cx24
Allelic
Composition
Tg(Camk2a-tTA)1Mmay/0
Tg(tetO-APPSwInd)885Dbo/0
Genetic
Background
involves: C3H/HeJ * C57BL/6 * CBA
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tg(Camk2a-tTA)1Mmay mutation (6 available)
Tg(tetO-APPSwInd)885Dbo mutation (0 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
nervous system
• mice exhibit a progressive neuronal atrophy that is most pronounced in the granule cell layer of hippocampal dentate gyrus (J:185792)
• mice exhibit a progressive neuronal atrophy that is most pronounced in the granule cell layer of hippocampal dentate gyrus (J:185792)
• mice exhibit a progressive neuronal atrophy that is most pronounced in the granule cell layer of hippocampal dentate gyrus (J:185792)
• however, when mice are reared on doxycycline, cell loss is not observed (J:185792)
• mice exhibit a progressive neuronal atrophy that is most pronounced in the granule cell layer of hippocampal dentate gyrus (J:185792)
• however, when mice are reared on doxycycline, cell loss is not observed (J:185792)
• mice produce transgenic APP protein at 10- to 30-fold over endogenous App levels (J:109829)
• expression of APPSw/Ind is higher relative to other three double transgenic lines, and suprression requires more doxycycline than the other three lines (J:109829)
• mice produce transgenic APP protein at 10- to 30-fold over endogenous App levels (J:109829)
• expression of APPSw/Ind is higher relative to other three double transgenic lines, and suprression requires more doxycycline than the other three lines (J:109829)

homeostasis/metabolism




Genotype
MGI:5448853
cx25
Allelic
Composition
Tg(Camk2a-tTA)1Mmay/0
Tg(tetO-TARDBP*)4Vle/0
Genetic
Background
involves: C3H/HeJ * C57BL/6J
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tg(Camk2a-tTA)1Mmay mutation (6 available)
Tg(tetO-TARDBP*)4Vle mutation (1 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
nervous system
• about 50% loss of dentate gyrus neurons at 1 month after Dox removal (J:170756)
• about 50% loss of dentate gyrus neurons at 1 month after Dox removal (J:170756)
• massive gliosis in cortical and hippocampal regions following Dox removal (J:170756)
• gliosis in the corticospinal tract, including the striatum, cerebral peduncles, medullary pyramids, and cervical spinal cord, following Dox removal (J:170756)
• massive gliosis in cortical and hippocampal regions following Dox removal (J:170756)
• gliosis in the corticospinal tract, including the striatum, cerebral peduncles, medullary pyramids, and cervical spinal cord, following Dox removal (J:170756)
• selective loss of corticospinal tract axons in cervical spinal cord associated with gliosis following Dox removal (J:170756)
• however, lower motor neuron loss is not observed (J:170756)
• selective loss of corticospinal tract axons in cervical spinal cord associated with gliosis following Dox removal (J:170756)
• however, lower motor neuron loss is not observed (J:170756)
• mutants rarely show accumulation of hyperphosphorylated, ubiquitinated cytoplasmic aggregates of TARDBP in neurons following Dox removal (around 1% of neurons showing aggregates) (J:170756)
• mutants rarely show accumulation of hyperphosphorylated, ubiquitinated cytoplasmic aggregates of TARDBP in neurons following Dox removal (around 1% of neurons showing aggregates) (J:170756)
• mutants switched to a doxycycline (dox)-free diet at 28 days of age show progressive neurodegeneration; neuron loss is particularly evident in the deep neocortical layers and in the dentate gyrus but is rarely seen in the hippocampal CA1 subfield and the olfactory bulb (J:170756)
• selective loss of corticospinal tract axons in cervical spinal cord following Dox removal (J:170756)
• mutants switched to a doxycycline (dox)-free diet at 28 days of age show progressive neurodegeneration; neuron loss is particularly evident in the deep neocortical layers and in the dentate gyrus but is rarely seen in the hippocampal CA1 subfield and the olfactory bulb (J:170756)
• selective loss of corticospinal tract axons in cervical spinal cord following Dox removal (J:170756)

behavior/neurological
• abnormal limb clasping as early as 1 week after dox removal that continues throughout life until sacrifice (J:170756)
• abnormal limb clasping as early as 1 week after dox removal that continues throughout life until sacrifice (J:170756)




Genotype
MGI:5448852
cx26
Allelic
Composition
Tg(Camk2a-tTA)1Mmay/0
Tg(tetO-TARDBP)12Vle/0
Genetic
Background
involves: C3H/HeJ * C57BL/6J
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tg(Camk2a-tTA)1Mmay mutation (6 available)
Tg(tetO-TARDBP)12Vle mutation (1 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
nervous system
• microglial activation is seen in the cortex and hippocampus as early as 1 month after Dox removal (J:170756)
• microglial activation is seen in the cortex and hippocampus as early as 1 month after Dox removal (J:170756)
• 6 months following Dox removal (J:170756)
• 6 months following Dox removal (J:170756)
• 20% loss of dentate gyrus neurons at 1 month and about 75% loss by 3 months after Dox removal (J:170756)
• 20% loss of dentate gyrus neurons at 1 month and about 75% loss by 3 months after Dox removal (J:170756)
• astrocytic activation is seen in the cortex and hippocampus as early as 1 month after Dox removal (J:170756)
• astrocytic activation is seen in the cortex and hippocampus as early as 1 month after Dox removal (J:170756)
• mutants switched to a doxycycline (Dox)-free diet at 28 days of age show progressive neurodegeneration, with neuron loss in the hippocampal dentate gyrus and neocortex beginning at about 1 month after Dox removal (J:170756)
• mutants switched to a doxycycline (Dox)-free diet at 28 days of age show progressive neurodegeneration, with neuron loss in the hippocampal dentate gyrus and neocortex beginning at about 1 month after Dox removal (J:170756)

behavior/neurological
• variable clasping behavior is seen approximately 1-3 months after Dox removal (J:170756)
• variable clasping behavior is seen approximately 1-3 months after Dox removal (J:170756)

hematopoietic system
• microglial activation is seen in the cortex and hippocampus as early as 1 month after Dox removal (J:170756)
• microglial activation is seen in the cortex and hippocampus as early as 1 month after Dox removal (J:170756)

immune system
• microglial activation is seen in the cortex and hippocampus as early as 1 month after Dox removal (J:170756)
• microglial activation is seen in the cortex and hippocampus as early as 1 month after Dox removal (J:170756)




Genotype
MGI:4420998
cx27
Allelic
Composition
Tg(Camk2a-tTA)1Mmay/0
Tg(tetO-LRRK2*)D10Cai/0
Tg(tetO-SNCA*A53T)E2Cai/0
Genetic
Background
involves: C57BL/6
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tg(Camk2a-tTA)1Mmay mutation (6 available)
Tg(tetO-LRRK2*)D10Cai mutation (0 available)
Tg(tetO-SNCA*A53T)E2Cai mutation (1 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
nervous system
• increasing accumulation of alpha-synuclein is detected in cell bodies at 1 month in A53T/KD mice compared to KD animals (J:156512)
• increasing accumulation of alpha-synuclein is detected in cell bodies at 1 month in A53T/KD mice compared to KD animals (J:156512)
• increased framentation of the Golgi complex is observed (J:156512)
• increased framentation of the Golgi complex is observed (J:156512)
• neuropathology is accelerated in A53T/KD mice compared to A53T mice (J:156512)
• neuropathology is accelerated in A53T/KD mice compared to A53T mice (J:156512)




Genotype
MGI:4421057
cx28
Allelic
Composition
Tg(Camk2a-tTA)1Mmay/0
Tg(tetO-SNCA)1Cai/0
Genetic
Background
involves: C57BL/6
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tg(Camk2a-tTA)1Mmay mutation (6 available)
Tg(tetO-SNCA)1Cai mutation (1 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
nervous system
N
• no alpha-synuclein accumulation is observed in neurons at 1 month (J:156512)
• no alpha-synuclein accumulation is observed in neurons at 1 month (J:156512)




Genotype
MGI:4420997
cx29
Allelic
Composition
Tg(Camk2a-tTA)1Mmay/0
Tg(tetO-LRRK2*)D10Cai/0
Genetic
Background
involves: C57BL/6
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tg(Camk2a-tTA)1Mmay mutation (6 available)
Tg(tetO-LRRK2*)D10Cai mutation (0 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
nervous system
• increased framentation of the Golgi complex is observed in KD mice (J:156512)
• increased framentation of the Golgi complex is observed in KD mice (J:156512)




Genotype
MGI:4420996
cx30
Allelic
Composition
Tg(Camk2a-tTA)1Mmay/0
Tg(tetO-LRRK2)C77Cai/0
Tg(tetO-SNCA*A53T)E2Cai/0
Genetic
Background
involves: C57BL/6
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tg(Camk2a-tTA)1Mmay mutation (6 available)
Tg(tetO-LRRK2)C77Cai mutation (0 available)
Tg(tetO-SNCA*A53T)E2Cai mutation (1 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
nervous system
• increasing accumulation of alpha-synuclein is detected in cell bodies in brains of A53T/LRRK2WT-L at 1 month compared to LRRK2WT-L animals (J:156512)
• increasing accumulation of alpha-synuclein is detected in cell bodies in brains of A53T/LRRK2WT-L at 1 month compared to LRRK2WT-L animals (J:156512)
• increased microglial activation is observed in the brain (J:156512)
• increased microglial activation is observed in the brain (J:156512)
• A53T/LRRK2WT-L mice show significant elevation of GFAP-positive astrocytes in the striatum compared to A53T mice (J:156512)
• A53T/LRRK2WT-L mice show significant elevation of GFAP-positive astrocytes in the striatum compared to A53T mice (J:156512)
• neurodegeneration is accelerated in the striatum (J:156512)
• neurodegeneration is accelerated in the striatum (J:156512)
• increasing accumulation of alpha-synuclein is detected in cell bodies at 1 month (J:156512)
• increasing accumulation of alpha-synuclein is detected in cell bodies at 1 month (J:156512)

behavior/neurological
• mice show no apparent motor phenotype up to 6 months of age (J:156512)
• mice show no apparent motor phenotype up to 6 months of age (J:156512)

hematopoietic system
• increased microglial activation is observed in the brain (J:156512)
• increased microglial activation is observed in the brain (J:156512)

immune system
• increased microglial activation is observed in the brain (J:156512)
• increased microglial activation is observed in the brain (J:156512)




Genotype
MGI:4420995
cx31
Allelic
Composition
Tg(Camk2a-tTA)1Mmay/0
Tg(tetO-LRRK2)C77Cai/0
Genetic
Background
involves: C57BL/6
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tg(Camk2a-tTA)1Mmay mutation (6 available)
Tg(tetO-LRRK2)C77Cai mutation (0 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
nervous system
N
• no neuronal degeneration is observed at 1 month in the striatum or cortex of LRRK2WT-L mice (J:156512)
• no neuronal degeneration is observed at 1 month in the striatum or cortex of LRRK2WT-L mice (J:156512)




Genotype
MGI:3776630
cx32
Allelic
Composition
Tg(Camk2a-tTA)1Mmay/0
Tg(tetO-S100a10)1Pggd/0
Genetic
Background
involves: C57BL/6
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tg(Camk2a-tTA)1Mmay mutation (6 available)
Tg(tetO-S100a10)1Pggd mutation (0 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
behavior/neurological
• mice exhibit decreased depression-related behavior such as immobility when suspended by their tails (J:104116)
• however, treatment with doxycycline restores normal depression-related behaviors (J:104116)
• mice exhibit decreased depression-related behavior such as immobility when suspended by their tails (J:104116)
• however, treatment with doxycycline restores normal depression-related behaviors (J:104116)
• mice exhibit decreased thigmotaxis and increased horizontal activity in an open-field test (J:104116)
• however, treatment with doxycycline restores normal anxiety-related behaviors (J:104116)
• mice exhibit decreased thigmotaxis and increased horizontal activity in an open-field test (J:104116)
• however, treatment with doxycycline restores normal anxiety-related behaviors (J:104116)




Genotype
MGI:4421001
cx33
Allelic
Composition
Tg(Camk2a-tTA)1Mmay/0
Tg(tetO-LRRK2)C7874Cai/0
Genetic
Background
involves: C57BL/6
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tg(Camk2a-tTA)1Mmay mutation (6 available)
Tg(tetO-LRRK2)C7874Cai mutation (2 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
nervous system
N
• no gross neuropathological phenotypes are observed in 12-month old animals (J:156512)
• no significant changes in neuron counts are observed compared to non-transgenic controls at the frontal cortex or dorsal striatum in 6- or 20-month old mice (J:156512)
• no gross neuropathological phenotypes are observed in 12-month old animals (J:156512)
• no significant changes in neuron counts are observed compared to non-transgenic controls at the frontal cortex or dorsal striatum in 6- or 20-month old mice (J:156512)
• the Golgi complex is drastically altered in neurons at 1 month, appearing thinner and fragmented (J:156512)
• at 6 months fragmentation of the cis-Golgi apparatus is similar to that in LRRK2WT and A53T/LRRK2 neurons (J:156512)
• at 1 month, the medial/trans-Golgi in neurons is significantly altered with ratio of fragmented trans-Golgi significantly increased compared to non-transgenic animals (J:156512)
• the Golgi complex is drastically altered in neurons at 1 month, appearing thinner and fragmented (J:156512)
• at 6 months fragmentation of the cis-Golgi apparatus is similar to that in LRRK2WT and A53T/LRRK2 neurons (J:156512)
• at 1 month, the medial/trans-Golgi in neurons is significantly altered with ratio of fragmented trans-Golgi significantly increased compared to non-transgenic animals (J:156512)




Genotype
MGI:4421002
cx34
Allelic
Composition
Tg(Camk2a-tTA)1Mmay/0
Tg(tetO-LRRK2)C7874Cai/0
Tg(tetO-SNCA*A53T)E2Cai/0
Genetic
Background
involves: C57BL/6
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tg(Camk2a-tTA)1Mmay mutation (6 available)
Tg(tetO-LRRK2)C7874Cai mutation (2 available)
Tg(tetO-SNCA*A53T)E2Cai mutation (1 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
nervous system
• increasing accumulation of alpha-synuclein is detected in cell bodies at 1 month compared to A53T/LRRK2WT-L animals (J:156512)
• increasing accumulation of alpha-synuclein is detected in cell bodies at 1 month compared to A53T/LRRK2WT-L animals (J:156512)
• increased microglial activation is observed in the brain (J:156512)
• increased microglial activation is observed in the brain (J:156512)
• neuron loss is detected at 6 months and later (J:156512)
• neuron loss is detected at 6 months and later (J:156512)
• A53T/LRRK2WT mice show significant elevation of GFAP-positive astrocytes in the striatum compared to A53T mice (J:156512)
• more GFAP-positive astrocytes are found in the brain than in A53T/LRRK2WT-L brains (J:156512)
• A53T/LRRK2WT mice show significant elevation of GFAP-positive astrocytes in the striatum compared to A53T mice (J:156512)
• more GFAP-positive astrocytes are found in the brain than in A53T/LRRK2WT-L brains (J:156512)
• the Golgi complex is drastically altered in neurons at 1 month with severely fragmented cis-Golgi (J:156512)
• at 1 month, the medial/trans-Golgi in neurons is severely fragmented (J:156512)
• the Golgi complex is drastically altered in neurons at 1 month with severely fragmented cis-Golgi (J:156512)
• at 1 month, the medial/trans-Golgi in neurons is severely fragmented (J:156512)
• neurodegeneration is accelerated in the striatum (J:156512)
• dramatic loss (>80%) of striatal neurons is seen in the dorsal striatum (J:156512)
• most degenerating neurons are striatal medium-sized spiny neurons (MSN) (J:156512)
• neurodegeneration is accelerated in the striatum (J:156512)
• dramatic loss (>80%) of striatal neurons is seen in the dorsal striatum (J:156512)
• most degenerating neurons are striatal medium-sized spiny neurons (MSN) (J:156512)
• neuropathology is accelerated in mice compared to A53T mice (J:156512)
• in 6 month old mice, elevated levels of ubiquitin are detected in somas and nuclei of cortical neurons; levels of alpha-synuclein and ubiquitin are slightly higher than in A53T mutant mice (J:156512)
• brain homogenates contain significantly elevated levels of ubiquitinated proteins at 3 months (J:156512)
• neuropathology is accelerated in mice compared to A53T mice (J:156512)
• in 6 month old mice, elevated levels of ubiquitin are detected in somas and nuclei of cortical neurons; levels of alpha-synuclein and ubiquitin are slightly higher than in A53T mutant mice (J:156512)
• brain homogenates contain significantly elevated levels of ubiquitinated proteins at 3 months (J:156512)

immune system
• increased microglial activation is observed in the brain (J:156512)
• increased microglial activation is observed in the brain (J:156512)

hematopoietic system
• increased microglial activation is observed in the brain (J:156512)
• increased microglial activation is observed in the brain (J:156512)




Genotype
MGI:4421003
cx35
Allelic
Composition
Tg(Camk2a-tTA)1Mmay/0
Tg(tetO-SNCA*A53T)E2Cai/0
Genetic
Background
involves: C57BL/6
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tg(Camk2a-tTA)1Mmay mutation (6 available)
Tg(tetO-SNCA*A53T)E2Cai mutation (1 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
growth/size/body
• A53T mice weigh significantly less than non transgenic mice and Tg(tetO-SNCA*A53T)E2Cai or Tg(Camk2a-tTA)1Mmay single mutants starting at 4 months of age (J:156512)
• A53T mice weigh significantly less than non transgenic mice and Tg(tetO-SNCA*A53T)E2Cai or Tg(Camk2a-tTA)1Mmay single mutants starting at 4 months of age (J:156512)

behavior/neurological
• mice display elevated rearing activities at 6 months of age (J:156512)
• mice display elevated rearing activities at 6 months of age (J:156512)
• at 2 months of age, mice show drastically increased ambulatory activity (J:156512)
• at 2 months of age, mice show drastically increased ambulatory activity (J:156512)

nervous system
• only a few neurons in the brain display alpha-synuclein staining in the cell body at 3 months; somatic accumulation becomes more prominent at 20 months; whereas no accumulation is detected in cell bodies at 1 month (J:156512)
• significant rescue of phenotype is observed when animals are treated with doxycycline to inhibit transgene expression (J:156512)
• only a few neurons in the brain display alpha-synuclein staining in the cell body at 3 months; somatic accumulation becomes more prominent at 20 months; whereas no accumulation is detected in cell bodies at 1 month (J:156512)
• significant rescue of phenotype is observed when animals are treated with doxycycline to inhibit transgene expression (J:156512)
• significant at 12 months (J:156512)
• significant rescue of phenotype is observed when animals are treated with doxycycline to inhibit transgene expression (J:156512)
• significant at 12 months (J:156512)
• significant rescue of phenotype is observed when animals are treated with doxycycline to inhibit transgene expression (J:156512)
• neuron loss is detected at 6 months and later (J:156512)
• significant rescue of phenotype is observed when animals are treated with doxycycline to inhibit transgene expression (J:156512)
• neuron loss is detected at 6 months and later (J:156512)
• significant rescue of phenotype is observed when animals are treated with doxycycline to inhibit transgene expression (J:156512)
• neuron loss is detected at 6 months and later (J:156512)
• in 6 month old mice but not in nontransgenic controls, elevated levels of ubiquitin are detected in somas and nuclei of cortical neurons, but (J:156512)
• neuron loss is detected at 6 months and later (J:156512)
• in 6 month old mice but not in nontransgenic controls, elevated levels of ubiquitin are detected in somas and nuclei of cortical neurons, but (J:156512)
• significant at 12 months (J:156512)
• significant rescue of phenotype is observed when animals are treated with doxycycline to inhibit transgene expression (J:156512)
• significant at 12 months (J:156512)
• significant rescue of phenotype is observed when animals are treated with doxycycline to inhibit transgene expression (J:156512)
• the Golgi complex is drastically altered in neurons at 1 month, appearing thinner and fragmented (J:156512)
• significant increase in Golgi fragmentation is observed at 6 months (J:156512)
• at 1 month, the medial/trans-Golgi in neurons is significantly altered with ratio of fragmented trans-Golgi significantly increased compared to non-transgenic animals (J:156512)
• significant rescue of phenotype is observed when animals are treated with doxycycline to inhibit transgene expression (J:156512)
• the Golgi complex is drastically altered in neurons at 1 month, appearing thinner and fragmented (J:156512)
• significant increase in Golgi fragmentation is observed at 6 months (J:156512)
• at 1 month, the medial/trans-Golgi in neurons is significantly altered with ratio of fragmented trans-Golgi significantly increased compared to non-transgenic animals (J:156512)
• significant rescue of phenotype is observed when animals are treated with doxycycline to inhibit transgene expression (J:156512)
• a significant increase in detergent-insoluble high molecular weight (HMW) alpha synuclein is detected in 12 month old mice compared to 1 month old mice (J:156512)
• significant decrease in HMW alpha-synuclein in total brain homogenates is observed when animals are treated with doxycycline to inhibit transgene expression (J:156512)
• a significant increase in detergent-insoluble high molecular weight (HMW) alpha synuclein is detected in 12 month old mice compared to 1 month old mice (J:156512)
• significant decrease in HMW alpha-synuclein in total brain homogenates is observed when animals are treated with doxycycline to inhibit transgene expression (J:156512)
• widespread degeneration is observed at 20 months (J:156512)
• age-dependent, progressive neurodegeneration occurs (J:156512)
• neuronal loss is detected in the frontal cortex (>80%) and dorsal striatum (>74%) at 20 months (J:156512)
• a significant reduction (>30%) of striatal neurons is seen at 6 months (J:156512)
• widespread degeneration is observed at 20 months (J:156512)
• age-dependent, progressive neurodegeneration occurs (J:156512)
• neuronal loss is detected in the frontal cortex (>80%) and dorsal striatum (>74%) at 20 months (J:156512)
• a significant reduction (>30%) of striatal neurons is seen at 6 months (J:156512)
• while 3-month old A53T mice show no abnormal neuropathology, but neuropathology is evident at 12 and 20 months (J:156512)
• in 6 month old mice, elevated levels of ubiquitin are detected in somas and nuclei of cortical neurons; at 20 monts, a punctate staining pattern at neuronal processes is observed (J:156512)
• brain homogenates contain significantly elevated levels of ubiquitinated proteins at 3 months (J:156512)
• while 3-month old A53T mice show no abnormal neuropathology, but neuropathology is evident at 12 and 20 months (J:156512)
• in 6 month old mice, elevated levels of ubiquitin are detected in somas and nuclei of cortical neurons; at 20 monts, a punctate staining pattern at neuronal processes is observed (J:156512)
• brain homogenates contain significantly elevated levels of ubiquitinated proteins at 3 months (J:156512)

hematopoietic system
• significant at 12 months (J:156512)
• significant rescue of phenotype is observed when animals are treated with doxycycline to inhibit transgene expression (J:156512)
• significant at 12 months (J:156512)
• significant rescue of phenotype is observed when animals are treated with doxycycline to inhibit transgene expression (J:156512)

immune system
• significant at 12 months (J:156512)
• significant rescue of phenotype is observed when animals are treated with doxycycline to inhibit transgene expression (J:156512)
• significant at 12 months (J:156512)
• significant rescue of phenotype is observed when animals are treated with doxycycline to inhibit transgene expression (J:156512)

cellular
• in striatal neurons at 1 month, numerous mitochondria have denser matrices and widened cristae compared to non-transgenic controls; these mitochondria are not functional (J:156512)
• in striatal neurons at 1 month, numerous mitochondria have denser matrices and widened cristae compared to non-transgenic controls; these mitochondria are not functional (J:156512)




Genotype
MGI:4421000
cx36
Allelic
Composition
Tg(Camk2a-tTA)1Mmay/0
Tg(tetO-LRRK2*G2019S)E3Cai/0
Tg(tetO-SNCA*A53T)E2Cai/0
Genetic
Background
involves: C57BL/6
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tg(Camk2a-tTA)1Mmay mutation (6 available)
Tg(tetO-LRRK2*G2019S)E3Cai mutation (1 available)
Tg(tetO-SNCA*A53T)E2Cai mutation (1 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
nervous system
• substantial accumulation of alpha-synuclein is detected in cell bodies at 1 month (J:156512)
• substantial accumulation of alpha-synuclein is detected in cell bodies at 1 month (J:156512)
• exacerbated in the striatum compared to A53T mice at 1 month of age (J:156512)
• levels of microglial activation are higher than in A53T/LRRK2WT mice (J:156512)
• exacerbated in the striatum compared to A53T mice at 1 month of age (J:156512)
• levels of microglial activation are higher than in A53T/LRRK2WT mice (J:156512)
• exacerbated in the striatum compared to A53T mice at 1 month of age (J:156512)
• levels of GFAP-positive cells are higher than in A53T/LRRK2WT mice (J:156512)
• exacerbated in the striatum compared to A53T mice at 1 month of age (J:156512)
• levels of GFAP-positive cells are higher than in A53T/LRRK2WT mice (J:156512)
• the Golgi complex is drastically altered in neurons at 1 month with severely fragmented (J:156512)
• at 1 month, the medial/trans-Golgi in neurons is severely fragmented (J:156512)
• the Golgi complex is drastically altered in neurons at 1 month with severely fragmented (J:156512)
• at 1 month, the medial/trans-Golgi in neurons is severely fragmented (J:156512)
• a significant increase in detergent-insoluble high molecular weight (HMW) alpha synuclein is detected in 1 month old mice compared to A53T age-matched mice (J:156512)
• a significant increase in detergent-insoluble high molecular weight (HMW) alpha synuclein is detected in 1 month old mice compared to A53T age-matched mice (J:156512)
• exacerbated in the striatum compared to A53T mice at 1 month of age (J:156512)
• dramatic loss (>85%) of striatal neurons is seen in the dorsal striatum (J:156512)
• exacerbated in the striatum compared to A53T mice at 1 month of age (J:156512)
• dramatic loss (>85%) of striatal neurons is seen in the dorsal striatum (J:156512)

hematopoietic system
• exacerbated in the striatum compared to A53T mice at 1 month of age (J:156512)
• levels of microglial activation are higher than in A53T/LRRK2WT mice (J:156512)
• exacerbated in the striatum compared to A53T mice at 1 month of age (J:156512)
• levels of microglial activation are higher than in A53T/LRRK2WT mice (J:156512)

immune system
• exacerbated in the striatum compared to A53T mice at 1 month of age (J:156512)
• levels of microglial activation are higher than in A53T/LRRK2WT mice (J:156512)
• exacerbated in the striatum compared to A53T mice at 1 month of age (J:156512)
• levels of microglial activation are higher than in A53T/LRRK2WT mice (J:156512)

cellular
• in striatal neurons at 1 month, numerous mitochondria have denser matrices and widened cristae compared to controls or A53T mice (seen with 3.5x greater frequency than in A53T mice); these mitochondria are not functional (J:156512)
• in striatal neurons at 1 month, numerous mitochondria have denser matrices and widened cristae compared to controls or A53T mice (seen with 3.5x greater frequency than in A53T mice); these mitochondria are not functional (J:156512)




Genotype
MGI:4421005
cx37
Allelic
Composition
Tg(Camk2a-tTA)1Mmay/0
Tg(tetO-LRRK2*G2019S)E3Cai/0
Tg(tetO-SNCA)1Cai/0
Genetic
Background
involves: C57BL/6
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tg(Camk2a-tTA)1Mmay mutation (6 available)
Tg(tetO-LRRK2*G2019S)E3Cai mutation (1 available)
Tg(tetO-SNCA)1Cai mutation (1 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
nervous system
• somatic alpha synuclein in neurons is apparent at 1 month (J:156512)
• somatic alpha synuclein in neurons is apparent at 1 month (J:156512)




Genotype
MGI:4420999
cx38
Allelic
Composition
Tg(Camk2a-tTA)1Mmay/0
Tg(tetO-LRRK2*G2019S)E3Cai/0
Genetic
Background
involves: C57BL/6
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tg(Camk2a-tTA)1Mmay mutation (6 available)
Tg(tetO-LRRK2*G2019S)E3Cai mutation (1 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
growth/size/body
• starting at 1 year, mice appear to gain less body weight than non-transgenic and Tg(tetO-LRRK2*G2019S)E3Cai single mutant mice, but are not different from Tg(Camk2a-tTA)1Mmay animals (J:156512)
• starting at 1 year, mice appear to gain less body weight than non-transgenic and Tg(tetO-LRRK2*G2019S)E3Cai single mutant mice, but are not different from Tg(Camk2a-tTA)1Mmay animals (J:156512)

behavior/neurological
N
• mice show normal performance in the rotarod test (J:156512)
• mice show normal performance in the rotarod test (J:156512)
• mice show significantly increased ambulatory activities starting at 12 months of age; at 12 months mice show a trend to increased rearing activities but this does not reach statistical significance (J:156512)
• mice show significantly increased ambulatory activities starting at 12 months of age; at 12 months mice show a trend to increased rearing activities but this does not reach statistical significance (J:156512)

nervous system
N
• no significant changes in neuron counts are observed compared to non-transgenic controls at the frontal cortex or dorsal striatum in 6- or 20-month old mice (J:156512)
• no increase in reactive astrocytosis or microglial activation are detected in the striatum or cortex at 20 months (J:156512)
• no alpha-synuclein accumulation is observed in neurons at 20 months (J:156512)
• no significant changes in neuron counts are observed compared to non-transgenic controls at the frontal cortex or dorsal striatum in 6- or 20-month old mice (J:156512)
• no increase in reactive astrocytosis or microglial activation are detected in the striatum or cortex at 20 months (J:156512)
• no alpha-synuclein accumulation is observed in neurons at 20 months (J:156512)
• the Golgi complex is drastically altered in neurons at 1 month, appearing thinner and fragmented (J:156512)
• at 6 months fragmentation of the cis-Golgi apparatus is similar to that in LRRK2WT and A53T/LRRK2 neurons (J:156512)
• at 1 month, the medial/trans-Golgi in neurons is significantly altered (J:156512)
• the Golgi complex is drastically altered in neurons at 1 month, appearing thinner and fragmented (J:156512)
• at 6 months fragmentation of the cis-Golgi apparatus is similar to that in LRRK2WT and A53T/LRRK2 neurons (J:156512)
• at 1 month, the medial/trans-Golgi in neurons is significantly altered (J:156512)
• brain homogenates moderately elevated levels of ubiquitinated proteins at 18 months compared to non-transgenic controls (J:156512)
• brain homogenates moderately elevated levels of ubiquitinated proteins at 18 months compared to non-transgenic controls (J:156512)




Genotype
MGI:5512702
cx39
Allelic
Composition
Tg(Camk2a-tTA)1Mmay/0
Tg(tetO-SNCA)0Olri/0
Genetic
Background
involves: C57BL/6
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tg(Camk2a-tTA)1Mmay mutation (6 available)
Tg(tetO-SNCA)0Olri mutation (0 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
behavior/neurological
• in the accelerated rotarod, mutants do not show short-term improvement between trial 1 and trial 2 as in controls, indicating impaired motor skill learning (J:132774)
• in the accelerated rotarod, mutants do not show short-term improvement between trial 1 and trial 2 as in controls, indicating impaired motor skill learning (J:132774)
• 52 week old mutants show impaired memory retention in the Morris water maze when tested 7 days later for their platform preference (J:132774)
• 52 week old mutants show impaired memory retention in the Morris water maze when tested 7 days later for their platform preference (J:132774)
• progressive impairment of motor performance that begins around 30 weeks of age (J:132774)
• progressive impairment of motor performance that begins around 30 weeks of age (J:132774)
• mice show impaired performance on the rotarod as early as 18 weeks of age, however progressive decline does not start before 30 weeks of age (J:132774)
• progressive motor decline is not reversed by treatment with doxycycline but it does halt further decline (J:132774)
• mice show impaired performance on the rotarod as early as 18 weeks of age, however progressive decline does not start before 30 weeks of age (J:132774)
• progressive motor decline is not reversed by treatment with doxycycline but it does halt further decline (J:132774)

nervous system
• mice show a 49% reduction of newly differentiated neurons in the granular cell layer of the dentate gyrus, and a reduction of DCX-positive neuroblasts, indicating impaired neurogenesis (J:132774)
• doxycycline treatment to inhibit transgene expression starting at 16 weeks of age does not result in reduced neurogenesis (J:132774)
• mice show a 49% reduction of newly differentiated neurons in the granular cell layer of the dentate gyrus, and a reduction of DCX-positive neuroblasts, indicating impaired neurogenesis (J:132774)
• doxycycline treatment to inhibit transgene expression starting at 16 weeks of age does not result in reduced neurogenesis (J:132774)
• total number of neuroblasts is reduced in the hippocampus (J:132774)
• total number of neuroblasts is reduced in the hippocampus (J:132774)
• reduction of dopamine level in the olfactory bulb in aged mice (J:132774)
• reduction of dopamine level in the olfactory bulb in aged mice (J:132774)
• dark cells in the substantia nigra and axonal pathology with condensed mitochondria and lipid droplets indicating degeneration of nigral cells (J:132774)
• dark cells in the substantia nigra and axonal pathology with condensed mitochondria and lipid droplets indicating degeneration of nigral cells (J:132774)
• large lipid-like drops are seen between nerve fibers of the pars reticulata (J:132774)
• large lipid-like drops are seen between nerve fibers of the pars reticulata (J:132774)
• dark degenerated pyramidal cells are scattered between unaffected neurons (J:132774)
• dark degenerated pyramidal cells are scattered between unaffected neurons (J:132774)
• reduction of dopaminergic neurons in the substantia nigra; degenerating cells are most prominent in the pars reticulata (J:132774)
• reduction of dopaminergic neurons in the substantia nigra; degenerating cells are most prominent in the pars reticulata (J:132774)
• reduction of dopamine trasnporter binding sites at presynaptic terminals (J:132774)
• reduction of dopamine trasnporter binding sites at presynaptic terminals (J:132774)
• degenerated neurons are seen in the hippocampus and substantia nigra, with darkened nuclear and cytoplasmic appearance, slightly collapsed nuclear envelope, and increased accumulation of lysosomes (J:132774)
• degenerated neurons are seen in the hippocampus and substantia nigra, with darkened nuclear and cytoplasmic appearance, slightly collapsed nuclear envelope, and increased accumulation of lysosomes (J:132774)
• proximal dendrites of the CA3 neurons show signs of degeneration (J:132774)
• dark cell degeneration in the CA1 pyramidal cells as well as in interneurons and granule cells of the dentate gyrus (J:132774)
• proximal dendrites of the CA3 neurons show signs of degeneration (J:132774)
• dark cell degeneration in the CA1 pyramidal cells as well as in interneurons and granule cells of the dentate gyrus (J:132774)
• many alpha-synuclein positive mossy fiber terminals, which may show swollen vesicles and enlarged mitochondria, form asymmetric contracts with immunonegative dendritic spines (J:132774)
• alpha-synuclein accumulates in the stratum lacunosum moleculare and in mossy fibers and their terminals (J:132774)
• many alpha-synuclein positive mossy fiber terminals, which may show swollen vesicles and enlarged mitochondria, form asymmetric contracts with immunonegative dendritic spines (J:132774)
• alpha-synuclein accumulates in the stratum lacunosum moleculare and in mossy fibers and their terminals (J:132774)

cellular
• mice show a 49% reduction of newly differentiated neurons in the granular cell layer of the dentate gyrus, and a reduction of DCX-positive neuroblasts, indicating impaired neurogenesis (J:132774)
• doxycycline treatment to inhibit transgene expression starting at 16 weeks of age does not result in reduced neurogenesis (J:132774)
• mice show a 49% reduction of newly differentiated neurons in the granular cell layer of the dentate gyrus, and a reduction of DCX-positive neuroblasts, indicating impaired neurogenesis (J:132774)
• doxycycline treatment to inhibit transgene expression starting at 16 weeks of age does not result in reduced neurogenesis (J:132774)
• total number of neuroblasts is reduced in the hippocampus (J:132774)
• total number of neuroblasts is reduced in the hippocampus (J:132774)

homeostasis/metabolism
• reduction of dopamine level in the olfactory bulb in aged mice (J:132774)
• reduction of dopamine level in the olfactory bulb in aged mice (J:132774)

Mouse Models of Human Disease
OMIM ID Ref(s)
Parkinson Disease, Late-Onset; PD 168600 J:132774




Genotype
MGI:5554193
cx40
Allelic
Composition
Tg(Camk2a-tTA)1Mmay/0
Tg(tetO-MAPT*K280,-luc)#Eman/0
Genetic
Background
involves: C57BL/6
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tg(Camk2a-tTA)1Mmay mutation (6 available)
Tg(tetO-MAPT*K280,-luc)#Eman mutation (0 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
nervous system
• tau tangles are seen as early as 2-3 months after doxycycline removal (at 6 weeks after birth to induce gene expression) in the entorhinal cortex and amygdala (J:131379)
• by 15 months after doxycycline removal, neurofibrillary tangles are seen in the neocortex (J:131379)
• neurofibrillary tangles persist in mice that are doxycycline treated for 4 months after 10 months of transgene expression (J:131379)
• tau tangles are seen as early as 2-3 months after doxycycline removal (at 6 weeks after birth to induce gene expression) in the entorhinal cortex and amygdala (J:131379)
• by 15 months after doxycycline removal, neurofibrillary tangles are seen in the neocortex (J:131379)
• neurofibrillary tangles persist in mice that are doxycycline treated for 4 months after 10 months of transgene expression (J:131379)
• tau aggregates are seen in the cortex as early as 2-3 months after doxycycline removal (at 6 weeks after birth to induce gene expression) (J:131379)
• tau aggregates include both endogenous and the exogenous tau protein (J:131379)
• when expression is switched off by addition of doxycycline, soluble and aggregated exogenous tau disappears within 1.5 months, however tangles of mouse tau remain (J:131379)
• tau aggregates are seen at 10 months after doxycycline removal to switch on expression (J:131379)
• moderate reduction in tau aggregates is seen in mice that express the transgene for 10 months and then are switched off with doxycycline treatment for 4 months (J:131379)
• exogenous tau disappears from tau aggregates in mice that express the transgene for 10 months and then are switched off with doxycycline treatment for 4 months (J:131379)
• missorting of tau into the somatodendritic compartment of cortical and hippocampal neurons is seen after doxycycline removal (J:131379)
• tau aggregates are seen in the cortex as early as 2-3 months after doxycycline removal (at 6 weeks after birth to induce gene expression) (J:131379)
• tau aggregates include both endogenous and the exogenous tau protein (J:131379)
• when expression is switched off by addition of doxycycline, soluble and aggregated exogenous tau disappears within 1.5 months, however tangles of mouse tau remain (J:131379)
• tau aggregates are seen at 10 months after doxycycline removal to switch on expression (J:131379)
• moderate reduction in tau aggregates is seen in mice that express the transgene for 10 months and then are switched off with doxycycline treatment for 4 months (J:131379)
• exogenous tau disappears from tau aggregates in mice that express the transgene for 10 months and then are switched off with doxycycline treatment for 4 months (J:131379)
• missorting of tau into the somatodendritic compartment of cortical and hippocampal neurons is seen after doxycycline removal (J:131379)
• astrogliosis is seen in the hilus region 21 months after doxycycline removal (J:131379)
• astrogliosis is seen in the hilus region 21 months after doxycycline removal (J:131379)
• activated astrocytes are detected inside the dentate gyrus after doxycycline removal, indicating inflammatory processes (J:169532)
• activated astrocytes are detected inside the dentate gyrus after doxycycline removal, indicating inflammatory processes (J:169532)
• by 15 months after doxycycline removal, dystrophic neurites are seen (J:131379)
• by 15 months after doxycycline removal, dystrophic neurites are seen (J:131379)
• loss of spine synapses and a decrease in presynaptic proteins in the hippocampus is seen after 9.5 months without doxycycline (J:131379)
• synapses decrease by about 30% after 10 months of expression (doxycycline removal) but only by about 15% when expression is then switched off with doxycycline treatment for 4 months, indicating some recovery of synapses (J:131379)
• loss of spine synapses and a decrease in presynaptic proteins in the hippocampus is seen after 9.5 months without doxycycline (J:131379)
• synapses decrease by about 30% after 10 months of expression (doxycycline removal) but only by about 15% when expression is then switched off with doxycycline treatment for 4 months, indicating some recovery of synapses (J:131379)
• some neurons that lack neurofibrillary tangles exhibit incipient degeneration as early as 2-3 months after doxycycline removal (J:131379)
• neuronal loss is seen in the granule cells of the dentate gyrus starting at 5 months after doxycycline removal and is increased at 24 months of gene expression such that shrinkage of the molecular layer is observed (J:131379)
• when expression is switched off again by addition of doxycycline for 1.5 months, the hippocampal pyramidal areas that retain neurofibrillary tangles display neuronal loss (J:131379)
• some neurons that lack neurofibrillary tangles exhibit incipient degeneration as early as 2-3 months after doxycycline removal (J:131379)
• neuronal loss is seen in the granule cells of the dentate gyrus starting at 5 months after doxycycline removal and is increased at 24 months of gene expression such that shrinkage of the molecular layer is observed (J:131379)
• when expression is switched off again by addition of doxycycline for 1.5 months, the hippocampal pyramidal areas that retain neurofibrillary tangles display neuronal loss (J:131379)
• neuronal loss is seen at 10 months after doxycycline removal in different regions of the hippocampus and cortex (J:169532)
• neuronal loss is seen in the CA1 and dentate gyrus region of the hippocampus in mice that express the transgene for 10 months and then are switched off with doxycycline treatment for 4 months (J:169532)
• neuronal loss is seen at 10 months after doxycycline removal in different regions of the hippocampus and cortex (J:169532)
• neuronal loss is seen in the CA1 and dentate gyrus region of the hippocampus in mice that express the transgene for 10 months and then are switched off with doxycycline treatment for 4 months (J:169532)
• mice at 10 months after doxycycline removal show reduced short term plasticity at the mossy fiber-CA3 synapse (J:169532)
• impairment of synaptic facilitation in mice at 10 months after doxycycline removal; this impairment is reversible after expression of the transgene is switched off with doxycycline treatment for 4 months (J:169532)
• mice at 10 months after doxycycline removal show reduced frequency facilitation induced by continuous stimulation at 1 Hz for 1 min; switching off transgene expression with doxycycline for 4 months partially restores the initial rising phase of frequency facilitation (J:169532)
• mice at 10 months after doxycycline removal show reduced short term plasticity at the mossy fiber-CA3 synapse (J:169532)
• impairment of synaptic facilitation in mice at 10 months after doxycycline removal; this impairment is reversible after expression of the transgene is switched off with doxycycline treatment for 4 months (J:169532)
• mice at 10 months after doxycycline removal show reduced frequency facilitation induced by continuous stimulation at 1 Hz for 1 min; switching off transgene expression with doxycycline for 4 months partially restores the initial rising phase of frequency facilitation (J:169532)
• LTP is impaired in CA3 and CA1 areas of the hippocampus in mice at 10 months after doxycycline removal; LTP is recovered after expression of the transgene is switched off with doxycycline treatment for 4 months (J:169532)
• LTP is impaired in CA3 and CA1 areas of the hippocampus in mice at 10 months after doxycycline removal; LTP is recovered after expression of the transgene is switched off with doxycycline treatment for 4 months (J:169532)
• posttetanic potentiation (PTP) is reduced in CA3 areas of the hippocampus in mice at 10 months after doxycycline removal; PTP is recovered after expression of the transgene is switched off with doxycycline treatment for 4 months (J:169532)
• posttetanic potentiation (PTP) is reduced in CA3 areas of the hippocampus in mice at 10 months after doxycycline removal; PTP is recovered after expression of the transgene is switched off with doxycycline treatment for 4 months (J:169532)

behavior/neurological
• mice at 10 months after doxycycline removal exhibit impaired memory in the passive avoidance test, reentering the dark compartment where mild footshock was introduced faster than controls which avoid the compartment (J:169532)
• mice at 10 months after doxycycline removal exhibit impaired memory in the passive avoidance test, reentering the dark compartment where mild footshock was introduced faster than controls which avoid the compartment (J:169532)
• in the Morris water maze task, mice 10 months after doxycycline removal show a slower rate of learning to find the submerged escape platform, especially at days 2 and 3 of training (J:169532)
• however, mice show normal behavior in the probe trial after the acquisition phase (J:169532)
• in reversal learning during which the platform is transferred to another quadrant, mice at 14 months after doxycycline removal are slower to reach the platform on days 2 and 3 compared to wild-type mice or mutant mice in which expression was turned off with doxycycline treatment for 4 months, and they spend more time searching the former target quadrant than the quadrant where the platform is now located (J:169532)
• in the Morris water maze task, mice 10 months after doxycycline removal show a slower rate of learning to find the submerged escape platform, especially at days 2 and 3 of training (J:169532)
• however, mice show normal behavior in the probe trial after the acquisition phase (J:169532)
• in reversal learning during which the platform is transferred to another quadrant, mice at 14 months after doxycycline removal are slower to reach the platform on days 2 and 3 compared to wild-type mice or mutant mice in which expression was turned off with doxycycline treatment for 4 months, and they spend more time searching the former target quadrant than the quadrant where the platform is now located (J:169532)
• lower rotarod performance at 10 months after doxycycline removal to induce expression, showing a lower performance on the first two trial but normal performance in the last trial (J:169532)
• however, grip strength and performance in spontaneous home cage activity is normal at 10 months after doxycycline removal (J:169532)
• lower rotarod performance at 10 months after doxycycline removal to induce expression, showing a lower performance on the first two trial but normal performance in the last trial (J:169532)
• however, grip strength and performance in spontaneous home cage activity is normal at 10 months after doxycycline removal (J:169532)

Mouse Models of Human Disease
OMIM ID Ref(s)
Alzheimer Disease; AD 104300 J:131379 , J:169532




Genotype
MGI:5554195
cx41
Allelic
Composition
Tg(Camk2a-tTA)1Mmay/0
Tg(tetO-MAPT*K280*I277P*I308P,-luc)#Eman/0
Genetic
Background
involves: C57BL/6
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tg(Camk2a-tTA)1Mmay mutation (6 available)
Tg(tetO-MAPT*K280*I277P*I308P,-luc)#Eman mutation (0 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
nervous system
N
• tau aggregates, neurofibrillary tangles, and neuron degeneration are not seen even after 22 months after doxycycline removal to induce gene expression (J:131379)
• tau aggregates, neurofibrillary tangles, and neuron degeneration are not seen even after 22 months after doxycycline removal to induce gene expression (J:131379)
(J:169532)
(J:169532)
• decrease in synaptic facilitation in mice at 10 months after doxycycline removal which is reversed upon doxycycline treatment to switch off expression (J:169532)
• mice at 10 months after doxycycline removal show reduced extent of frequency facilitation (J:169532)
• decrease in synaptic facilitation in mice at 10 months after doxycycline removal which is reversed upon doxycycline treatment to switch off expression (J:169532)
• mice at 10 months after doxycycline removal show reduced extent of frequency facilitation (J:169532)
• posttetanic potentiation (PTP) is reduced in CA3 areas of the hippocampus in mice at 10 months after doxycycline removal, however LTP is normal (J:169532)
• posttetanic potentiation (PTP) is reduced in CA3 areas of the hippocampus in mice at 10 months after doxycycline removal, however LTP is normal (J:169532)
• paired-pulse facilitation (PPF) is altered at the 10 and 20 ms interval in CA1 region of the hippocampus (J:169532)
• paired-pulse facilitation (PPF) is altered at the 10 and 20 ms interval in CA1 region of the hippocampus (J:169532)




Genotype
MGI:3700230
cx42
Allelic
Composition
Tg(Camk2a-tTA)1Mmay/0
Tg(tetO-COX8A/EYFP)1Ksn/0
Genetic
Background
involves: C57BL/6
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tg(Camk2a-tTA)1Mmay mutation (6 available)
Tg(tetO-COX8A/EYFP)1Ksn mutation (1 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
normal phenotype
• mice appear normal and healthy, and expression of EYFP is detected in neuronal mitochondria under appropriate conditions (J:118452)
• mice appear normal and healthy, and expression of EYFP is detected in neuronal mitochondria under appropriate conditions (J:118452)




Genotype
MGI:5694057
cx43
Allelic
Composition
Tg(Camk2a-tTA)1Mmay/0
Tg(tetO-DRD3)3-10Kndl/0
Genetic
Background
involves: C57BL/6 * CBA
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tg(Camk2a-tTA)1Mmay mutation (6 available)
Tg(tetO-DRD3)3-10Kndl mutation (1 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
behavior/neurological
• reduced number of total lever presses in progressive ratio (PR) measure of incentive motivation (J:225565)
• mice exhibit less motivation to obtain food reward (J:225565)
• reduced number of total lever presses in progressive ratio (PR) measure of incentive motivation (J:225565)
• mice exhibit less motivation to obtain food reward (J:225565)




Genotype
MGI:3851446
cx44
Allelic
Composition
Tg(Camk2a-tTA)1Mmay/0
Tg(tetO-HTT*94Q,-lacZ)1Rhn/0
Genetic
Background
involves: C57BL/6 * CBA
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tg(Camk2a-tTA)1Mmay mutation (6 available)
Tg(tetO-HTT*94Q,-lacZ)1Rhn mutation (0 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
mortality/aging
• some mice die between 8 to 10 months due to injuries sustain from fighting with other mice (J:61490)
• some mice die between 8 to 10 months due to injuries sustain from fighting with other mice (J:61490)
• fewer than expected mice are recovered due to prenatal lethality (J:61490)
• however, treatment of pregnant dams with doxycycline eliminates prenatal lethality (J:61490)
• fewer than expected mice are recovered due to prenatal lethality (J:61490)
• however, treatment of pregnant dams with doxycycline eliminates prenatal lethality (J:61490)

nervous system
• ventricles are enlarged compared to in wild-type mice (J:61490)
• ventricles are enlarged compared to in wild-type mice (J:61490)
• the striatum is reduced in size compared to in wild-type mice (J:61490)
• the ventricular zone of the striatum is narrower than in wild-type mice (J:61490)
• the striatum is reduced in size compared to in wild-type mice (J:61490)
• the ventricular zone of the striatum is narrower than in wild-type mice (J:61490)
• the area of the caudate putamen is reduced compared to in wild-type mice (J:61490)
• however, treatment with doxycycline after the onset of symptoms restores some of the caudate putamen area (J:61490)
• the area of the caudate putamen is reduced compared to in wild-type mice (J:61490)
• however, treatment with doxycycline after the onset of symptoms restores some of the caudate putamen area (J:61490)
• gliosis spreads throughout the lateral and medial striatum over time (J:61490)
• gliosis spreads throughout the lateral and medial striatum over time (J:61490)
• mice exhibit reactive astrocytosis in the striatum that spreads over time (J:61490)
• however, treatment with doxycycline after the onset of symptoms reduces astrocytosis (J:61490)
• mice exhibit reactive astrocytosis in the striatum that spreads over time (J:61490)
• however, treatment with doxycycline after the onset of symptoms reduces astrocytosis (J:61490)
• mice develop neuronal intranuclear and extranuclear inclusion (J:61490)
• however, treatment with doxycycline after the onset of symptoms alleviates inclusions (J:61490)
• mice develop neuronal intranuclear and extranuclear inclusion (J:61490)
• however, treatment with doxycycline after the onset of symptoms alleviates inclusions (J:61490)

behavior/neurological
• in older mice with tremors (J:61490)
• in older mice with tremors (J:61490)
• beginning at 4 weeks, some mice exhibit limb grasping when suspended (J:61490)
• by 8 weeks, all mice display clasping that can last after mice are released (J:61490)
• however, treatment with doxycycline after the onset of symptoms reduces glasping behavior and duration (J:61490)
• beginning at 4 weeks, some mice exhibit limb grasping when suspended (J:61490)
• by 8 weeks, all mice display clasping that can last after mice are released (J:61490)
• however, treatment with doxycycline after the onset of symptoms reduces glasping behavior and duration (J:61490)
• mild tremors begin at 20 weeks in some mice (J:61490)
• in some mice tremors develop into a jerking motion (J:61490)
• mild tremors begin at 20 weeks in some mice (J:61490)
• in some mice tremors develop into a jerking motion (J:61490)
• mice exhibit progressive motor dysfunction with choreic and dystonic movements, and parkinsonism (J:61490)
• mice exhibit progressive motor dysfunction with choreic and dystonic movements, and parkinsonism (J:61490)
• at 36 weeks (J:61490)
• at 36 weeks (J:61490)

muscle
• mice exhibit progressive motor dysfunction with choreic and dystonic movements, and parkinsonism (J:61490)
• mice exhibit progressive motor dysfunction with choreic and dystonic movements, and parkinsonism (J:61490)

Mouse Models of Human Disease
OMIM ID Ref(s)
Huntington Disease; HD 143100 J:61490




Genotype
MGI:3838963
cx45
Allelic
Composition
Tg(Camk2a-tTA)1Mmay/0
Tg(tetO-DISC1*)1001Plet/0
Genetic
Background
involves: C57BL/6 * CBA * SJL
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tg(Camk2a-tTA)1Mmay mutation (6 available)
Tg(tetO-DISC1*)1001Plet mutation (1 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
behavior/neurological
• spatial memory in females is impaired in probe trials, with females spending less time in the target quadrant where the platform had previously been (J:146881)
• spatial memory in females is impaired in probe trials, with females spending less time in the target quadrant where the platform had previously been (J:146881)
• male mutants show higher degree of spontaneous locomotor activity than wild-type littermate controls during a 20-hour period (J:146881)
• male mutants show higher degree of spontaneous locomotor activity than wild-type littermate controls during a 20-hour period (J:146881)
• male mutants spend significantly less time in non-aggressive social interaction with other males (J:146881)
• male mutants spend significantly less time in non-aggressive social interaction with other males (J:146881)
• males display increased aggressiveness toward other males, with an increase in number of attacks (J:146881)
• males display increased aggressiveness toward other males, with an increase in number of attacks (J:146881)

nervous system
• volume is significantly increased, with no change in total brain volume (J:146881)
• volume is significantly increased, with no change in total brain volume (J:146881)
• cultured control neurons grow more complex neurite arbors than mutant neurons (for 20-100 um rings centered on neuron soma) (J:146881)
• cultured control neurons grow more complex neurite arbors than mutant neurons (for 20-100 um rings centered on neuron soma) (J:146881)




Genotype
MGI:5316005
cx46
Allelic
Composition
Tg(Camk2a-tTA)1Mmay/0
Tg(tetO-COX8A/PstI*)1Ctm/0
Genetic
Background
involves: C57BL/6 * CBA * SJL
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tg(Camk2a-tTA)1Mmay mutation (6 available)
Tg(tetO-COX8A/PstI*)1Ctm mutation (0 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
mortality/aging
• mutants grown in the presence of Dox from E0 to P21 become progressively less active after the removal of Dox and die before 100 days of age (J:145737)
• mutants grown in the presence of Dox from E0 to P21 become progressively less active after the removal of Dox and die before 100 days of age (J:145737)

behavior/neurological
• mutants grown in the absence of Dox develop an abnormal limb-clasping behavior at 2 months of age (J:145737)
• mutants grown in the presence of Dox from E0 to P21, however, do not exhibit this limb-clasping behavior (J:145737)
• mutants grown in the absence of Dox develop an abnormal limb-clasping behavior at 2 months of age (J:145737)
• mutants grown in the presence of Dox from E0 to P21, however, do not exhibit this limb-clasping behavior (J:145737)
• mutants grown in the presence of Dox from E0 to P21 become progressively less active after the removal of Dox and die before 100 days of age (J:145737)
• mutants grown in the presence of Dox from E0 to P21 become progressively less active after the removal of Dox and die before 100 days of age (J:145737)




Genotype
MGI:5634716
cx47
Allelic
Composition
Tg(Camk2a-tTA)1Mmay/0
Tg(tetO-Mtor*)#Atai/0
Genetic
Background
involves: C57BL/6 * DBA/2 * ICR
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tg(Camk2a-tTA)1Mmay mutation (6 available)
Tg(tetO-Mtor*)#Atai mutation (0 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
behavior/neurological
• withdrawal of doxycycline after administrating it for the first three weeks of life results in hypoactivity from 6 weeks of age (J:211789)
• withdrawal of doxycycline after administrating it for the first three weeks of life results in hypoactivity from 6 weeks of age (J:211789)
• in the absence of doxycycline, mice show spontaneous behavioral seizures around 2 weeks of age accompanied by abnormal local field potentials (J:211789)
• mice exhibit frequent spontaneous seizures 3-4 weeks after withdrawal of doxycycline; seizures are characterized by unilateral forelimb clonus followed by bilateral forelimb clonus and falling, and differences in local field potentials between the right and left cortices (J:211789)
• administration of doxycycline or rapamycin suppresses epileptic seizures (J:211789)
• in the absence of doxycycline, mice show spontaneous behavioral seizures around 2 weeks of age accompanied by abnormal local field potentials (J:211789)
• mice exhibit frequent spontaneous seizures 3-4 weeks after withdrawal of doxycycline; seizures are characterized by unilateral forelimb clonus followed by bilateral forelimb clonus and falling, and differences in local field potentials between the right and left cortices (J:211789)
• administration of doxycycline or rapamycin suppresses epileptic seizures (J:211789)

growth/size/body
• in the absence of doxycycline, mice show macrocephaly with abnormal cortical cytoarchitecture (J:211789)
• withdrawal of doxycycline after administrating it for the first three weeks of life results is macrocephaly without affecting the arrangement of the cortical layer (J:211789)
• in the absence of doxycycline, mice show macrocephaly with abnormal cortical cytoarchitecture (J:211789)
• withdrawal of doxycycline after administrating it for the first three weeks of life results is macrocephaly without affecting the arrangement of the cortical layer (J:211789)
• in the absence of doxycycline, mice exhibit severe growth retardation from P10 (J:211789)
• in the absence of doxycycline, mice exhibit severe growth retardation from P10 (J:211789)

hematopoietic system
• in the absence of doxycycline, mice exhibit an increased number of microglial cells with enlarged cell bodies and short processes in the cortex (J:211789)
• withdrawal of doxycycline after administrating it for the first three weeks of life results in an increased number of microglial cells with enlarged cell bodies and short processes (J:211789)
• in the absence of doxycycline, mice exhibit an increased number of microglial cells with enlarged cell bodies and short processes in the cortex (J:211789)
• withdrawal of doxycycline after administrating it for the first three weeks of life results in an increased number of microglial cells with enlarged cell bodies and short processes (J:211789)

immune system
• in the absence of doxycycline, mice exhibit an increased number of microglial cells with enlarged cell bodies and short processes in the cortex (J:211789)
• withdrawal of doxycycline after administrating it for the first three weeks of life results in an increased number of microglial cells with enlarged cell bodies and short processes (J:211789)
• in the absence of doxycycline, mice exhibit an increased number of microglial cells with enlarged cell bodies and short processes in the cortex (J:211789)
• withdrawal of doxycycline after administrating it for the first three weeks of life results in an increased number of microglial cells with enlarged cell bodies and short processes (J:211789)

mortality/aging
• in the absence of doxycycline, mice die at 15-20 days of age (J:211789)
• in the absence of doxycycline, mice die at 15-20 days of age (J:211789)
• withdrawal of doxycline after administrating it for the first three weeks of life results is death between 6 and 7 weeks of age (J:211789)
• administration of doxycycline or rapamycin suppresses lethality (J:211789)
• withdrawal of doxycline after administrating it for the first three weeks of life results is death between 6 and 7 weeks of age (J:211789)
• administration of doxycycline or rapamycin suppresses lethality (J:211789)

nervous system
• in the absence of doxycycline, mice show spontaneous behavioral seizures around 2 weeks of age accompanied by abnormal local field potentials (J:211789)
• mice exhibit frequent spontaneous seizures 3-4 weeks after withdrawal of doxycycline; seizures are characterized by unilateral forelimb clonus followed by bilateral forelimb clonus and falling, and differences in local field potentials between the right and left cortices (J:211789)
• administration of doxycycline or rapamycin suppresses epileptic seizures (J:211789)
• in the absence of doxycycline, mice show spontaneous behavioral seizures around 2 weeks of age accompanied by abnormal local field potentials (J:211789)
• mice exhibit frequent spontaneous seizures 3-4 weeks after withdrawal of doxycycline; seizures are characterized by unilateral forelimb clonus followed by bilateral forelimb clonus and falling, and differences in local field potentials between the right and left cortices (J:211789)
• administration of doxycycline or rapamycin suppresses epileptic seizures (J:211789)
• in the absence of doxycycline, mice exhibit an increased number of microglial cells with enlarged cell bodies and short processes in the cortex (J:211789)
• withdrawal of doxycycline after administrating it for the first three weeks of life results in an increased number of microglial cells with enlarged cell bodies and short processes (J:211789)
• in the absence of doxycycline, mice exhibit an increased number of microglial cells with enlarged cell bodies and short processes in the cortex (J:211789)
• withdrawal of doxycycline after administrating it for the first three weeks of life results in an increased number of microglial cells with enlarged cell bodies and short processes (J:211789)
• cortical hypertrophy is seen at P12 in the absence of doxycycline (J:211789)
• in the absence of doxycycline, cortical lamination is disrupted (J:211789)
• withdrawal of doxycycline after administrating it for the first three weeks of life results in cortical hypertrophy at 6-7 weeks of age, however, cortical lamination is preserved (J:211789)
• administration of doxycycline or rapamycin suppresses cortical hypertrophy (J:211789)
• cortical hypertrophy is seen at P12 in the absence of doxycycline (J:211789)
• in the absence of doxycycline, cortical lamination is disrupted (J:211789)
• withdrawal of doxycycline after administrating it for the first three weeks of life results in cortical hypertrophy at 6-7 weeks of age, however, cortical lamination is preserved (J:211789)
• administration of doxycycline or rapamycin suppresses cortical hypertrophy (J:211789)
• in the absence of doxycycline, cortical thickness is increased (J:211789)
• withdrawal of doxycycline after administrating it for the first three weeks of life results in thickened cerebral cortex at 6-7 weeks of age (J:211789)
• in the absence of doxycycline, cortical thickness is increased (J:211789)
• withdrawal of doxycycline after administrating it for the first three weeks of life results in thickened cerebral cortex at 6-7 weeks of age (J:211789)
• in the absence of doxycycline, soma size of cortical neurons is increased (J:211789)
• withdrawal of doxycycline after administrating it for the first three weeks of life results in enlarged cortical neuronal soma at 6-7 weeks of age (J:211789)
• in the absence of doxycycline, soma size of cortical neurons is increased (J:211789)
• withdrawal of doxycycline after administrating it for the first three weeks of life results in enlarged cortical neuronal soma at 6-7 weeks of age (J:211789)
• in the absence of doxycycline, mice exhibit an accumulation of ubiquitin-positive inclusions in neurons of the cortex at P2 (J:211789)
• withdrawal of doxycycline after administrating it for the first three weeks of life results in ubiquitin-positive cytoplasmic inclusions in many neurons of the cortex, specially in the pyramidal neurons in layers II/III and V (J:211789)
• in the absence of doxycycline, mice exhibit an accumulation of ubiquitin-positive inclusions in neurons of the cortex at P2 (J:211789)
• withdrawal of doxycycline after administrating it for the first three weeks of life results in ubiquitin-positive cytoplasmic inclusions in many neurons of the cortex, specially in the pyramidal neurons in layers II/III and V (J:211789)
• mice exhibit neurodegeneration after doxycycline removal (J:211789)
• mice exhibit neurodegeneration after doxycycline removal (J:211789)




Genotype
MGI:3653709
cx48
Allelic
Composition
Tg(Camk2a-tTA)1Mmay/0
Tg(tetO-CDK5R1/GFP)337Lht/0
Genetic
Background
involves: C57BL/6J
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tg(Camk2a-tTA)1Mmay mutation (6 available)
Tg(tetO-CDK5R1/GFP)337Lht mutation (1 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
growth/size/body
• transgenic mice with transgene expression induced by removal of doxycycline from their food 4-6 weeks postnatal exhibit a slightly decreased body weight compared to control littermates (J:104240)
• transgenic mice with transgene expression induced by removal of doxycycline from their food 4-6 weeks postnatal exhibit a slightly decreased body weight compared to control littermates (J:104240)

nervous system
• mice with transgene expression induced by removal of doxycycline from the food 4-6 weeks postnatal exhibit amyloid beta deposits in the hippocampus (J:177847)
• mice with transgene expression induced by removal of doxycycline from the food 4-6 weeks postnatal exhibit amyloid beta deposits in the hippocampus (J:177847)
• transgenic mice with induction of expression of the transgene for different time periods display progressive decrease in brain weight; with induction for 5 weeks there is a 15-20% decrease in brain weight and with more than 12 weeks of induction, the weight decrease is 30% (J:104240)
• transgenic mice with induction of expression of the transgene for different time periods display progressive decrease in brain weight; with induction for 5 weeks there is a 15-20% decrease in brain weight and with more than 12 weeks of induction, the weight decrease is 30% (J:104240)
• in transgenic mice induced for 8 and 12 weeks, there is an increase in aggregations of tau protein (insoluble tau) with an increased amount of phosphorylated tau present; at 15 weeks, there is less soluble tau than in wild-type forebrains and similar results are found at 27 weeks of induction (J:104240)
• in transgenic mice induced for 8 and 12 weeks, there is an increase in aggregations of tau protein (insoluble tau) with an increased amount of phosphorylated tau present; at 15 weeks, there is less soluble tau than in wild-type forebrains and similar results are found at 27 weeks of induction (J:104240)
• brains of transgenic mice induced for 12 weeks show a significant decrease in thickness and neuronal density in the hippocampus compared to controls (J:104240)
• brains of transgenic mice induced for 12 weeks show a significant decrease in thickness and neuronal density in the hippocampus compared to controls (J:104240)
• 50% reduction in the number of NeuN-positive cells in hippocampal area CA1 in 6-week induced mice (J:177847)
• 50% reduction in the number of NeuN-positive cells in hippocampal area CA1 in 6-week induced mice (J:177847)
• brains of transgenic mice induced for 12 weeks show a significant decrease in thickness and neuronal density in the cerebral cortex compared to controls; mice induced for 8 or 12 weeks show a 25 or 40% decrease in cortical neuronal density, respectively, whereas wild-type or non-induced transgenic mice had the same neuronal density (J:104240)
• brains of transgenic mice induced for 12 weeks show a significant decrease in thickness and neuronal density in the cerebral cortex compared to controls; mice induced for 8 or 12 weeks show a 25 or 40% decrease in cortical neuronal density, respectively, whereas wild-type or non-induced transgenic mice had the same neuronal density (J:104240)
• induced transgenic mice at 12 weeks postnatal display significant forebrain atrophy with decrease in forebrain mass (J:104240)
• induced transgenic mice at 12 weeks postnatal display significant forebrain atrophy with decrease in forebrain mass (J:104240)
• neurofibrillary tangle-like pathology is exhibited in brains of transgenic mice induced for 27 weeks; there are numerous intraneuronal and flame-shaped neurons positive for neurofibrillary tangle-specific proteins in the cortex and hippocampus of transgenic mice but not wild-type (J:104240)
• other methosds also identify neurofibrillary tangle-like structures in the cerebral cortex, hippocampus and entorhinal cortex of transgenic mice (J:104240)
• brains of transgenic mice induced for 8 or 12 weeks do not express markers for late stage tangles similar to what is observed in wild-type (J:104240)
• neurofibrillary tangle-like pathology is exhibited in brains of transgenic mice induced for 27 weeks; there are numerous intraneuronal and flame-shaped neurons positive for neurofibrillary tangle-specific proteins in the cortex and hippocampus of transgenic mice but not wild-type (J:104240)
• other methosds also identify neurofibrillary tangle-like structures in the cerebral cortex, hippocampus and entorhinal cortex of transgenic mice (J:104240)
• brains of transgenic mice induced for 8 or 12 weeks do not express markers for late stage tangles similar to what is observed in wild-type (J:104240)
• reactive astrogliosis is increased throughout the cortex and hippocampus of mutants evident by an increase in radial and stellate-shaped astrocytes (J:104240)
• reactive astrogliosis is increased throughout the cortex and hippocampus of mutants evident by an increase in radial and stellate-shaped astrocytes (J:104240)
• reactive astrogliosis is seen in the cortex and hippocampus in 6-week induced mice (J:177847)
• reactive astrogliosis is seen in the cortex and hippocampus in 6-week induced mice (J:177847)
• mice exhibit reduced density of synaptophysin puncta in the stratum radiatum of the hippocampus, indicating reduced synapse density following a 6-week induction (J:177847)
• mice exhibit reduced density of synaptophysin puncta in the stratum radiatum of the hippocampus, indicating reduced synapse density following a 6-week induction (J:177847)
• mice exhibit impaired synaptic plasticity following a 6-week induction (J:177847)
• mice exhibit impaired synaptic plasticity following a 6-week induction (J:177847)
• mice exhibit diminished CA1 long term potentiation (LTP) following a 6-week induction (J:177847)
• mice exhibit diminished CA1 long term potentiation (LTP) following a 6-week induction (J:177847)

behavior/neurological
• associative learning in contextual fear conditioning is impaired in 6-week induced mice, with mice spending less time freezing after training than wild-type mice (J:177847)
• associative learning in contextual fear conditioning is impaired in 6-week induced mice, with mice spending less time freezing after training than wild-type mice (J:177847)

homeostasis/metabolism
• mice with transgene expression induced by removal of doxycycline from the food 4-6 weeks postnatal exhibit amyloid beta deposits in the hippocampus (J:177847)
• mice with transgene expression induced by removal of doxycycline from the food 4-6 weeks postnatal exhibit amyloid beta deposits in the hippocampus (J:177847)

Mouse Models of Human Disease
OMIM ID Ref(s)
Alzheimer Disease; AD 104300 J:177847




Genotype
MGI:5555966
cx49
Allelic
Composition
Tg(Camk2a-tTA)1Mmay/0
Tg(tetO-Rai1,-EGFP)463Walz/0
Genetic
Background
involves: C57BL/6J * CBA/J
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tg(Camk2a-tTA)1Mmay mutation (6 available)
Tg(tetO-Rai1,-EGFP)463Walz mutation (0 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
growth/size/body
• mutants start to show lower weight at 4 months of age (J:207141)
• mutants start to show lower weight at 4 months of age (J:207141)

behavior/neurological
• mutants show less freezing in the contextual fear test, indicating that learning and/or memory are impaired (J:207141)
• mutants show less freezing in the contextual fear test, indicating that learning and/or memory are impaired (J:207141)
• mutants show less freezing in the sound cued fear tests, indicating that learning and/or memory are impaired (J:207141)
• mutants show less freezing in the sound cued fear tests, indicating that learning and/or memory are impaired (J:207141)
• in the open field, mutants show an increase in total distance traveled indicating hyperactivity (J:207141)
• however anxiety-like behavior is not observed and mice show normal sociability and preference for social novelty (J:207141)
• in the open field, mutants show an increase in total distance traveled indicating hyperactivity (J:207141)
• however anxiety-like behavior is not observed and mice show normal sociability and preference for social novelty (J:207141)
• lower percentage of vocalization, with mutants showing 17% vocalization compared to 29% in wild-type mice (J:207141)
• lower percentage of vocalization, with mutants showing 17% vocalization compared to 29% in wild-type mice (J:207141)

adipose tissue

Mouse Models of Human Disease
OMIM ID Ref(s)
Potocki-Lupski Syndrome; PTLS 610883 J:207141




Genotype
MGI:5555967
cx50
Allelic
Composition
Tg(Camk2a-tTA)1Mmay/0
Tg(tetO-Rai1,-EGFP)479Walz/0
Genetic
Background
involves: C57BL/6J * CBA/J
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tg(Camk2a-tTA)1Mmay mutation (6 available)
Tg(tetO-Rai1,-EGFP)479Walz mutation (0 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
growth/size/body
• mutants start to show lower weight at 2 months of age (J:207141)
• mutants treated with Dox to turn off transgene expression from conception to 3 months of age show normal weight (J:207141)
• Dox administration from 1 to 3 months of age to turn off transgene expression before the onset of abnormalities is seen does not prevent abnormal phenotypes, with mutants developing lower weight from 9 weeks of age (J:207141)
• Dox administration from 3 to 5 months of age to turn off transgene expression after the onset of abnormal phenotypes does not result in recovery after 2 months of Dox treatment (J:207141)
• mutants start to show lower weight at 2 months of age (J:207141)
• mutants treated with Dox to turn off transgene expression from conception to 3 months of age show normal weight (J:207141)
• Dox administration from 1 to 3 months of age to turn off transgene expression before the onset of abnormalities is seen does not prevent abnormal phenotypes, with mutants developing lower weight from 9 weeks of age (J:207141)
• Dox administration from 3 to 5 months of age to turn off transgene expression after the onset of abnormal phenotypes does not result in recovery after 2 months of Dox treatment (J:207141)

behavior/neurological
• mutants show less freezing in the contextual fear test, indicating that learning and/or memory are impaired (J:207141)
• mutants treated with Dox to turn off transgene expression from conception to 3 months of age show normal contextual memory (J:207141)
• Dox administration from 1 to 3 months of age to turn off transgene expression before the onset of abnormalities is seen does not prevent abnormal phenotypes, with mutants developing impaired learning and memory in the fear contextual conditioning test (J:207141)
• mutants show less freezing in the contextual fear test, indicating that learning and/or memory are impaired (J:207141)
• mutants treated with Dox to turn off transgene expression from conception to 3 months of age show normal contextual memory (J:207141)
• Dox administration from 1 to 3 months of age to turn off transgene expression before the onset of abnormalities is seen does not prevent abnormal phenotypes, with mutants developing impaired learning and memory in the fear contextual conditioning test (J:207141)
• mutants show less freezing in the sound cued fear tests, indicating that learning and/or memory are impaired (J:207141)
• mutants treated with Dox to turn off transgene expression from conception to 3 months of age still show impaired memory in the sound cue test (J:207141)
• Dox administration from 1 to 3 months of age to turn off transgene expression before the onset of abnormalities is seen does not prevent abnormal phenotypes, with mutants developing impaired learning and memory in the cued conditioning tests (J:207141)
• mutants show less freezing in the sound cued fear tests, indicating that learning and/or memory are impaired (J:207141)
• mutants treated with Dox to turn off transgene expression from conception to 3 months of age still show impaired memory in the sound cue test (J:207141)
• Dox administration from 1 to 3 months of age to turn off transgene expression before the onset of abnormalities is seen does not prevent abnormal phenotypes, with mutants developing impaired learning and memory in the cued conditioning tests (J:207141)
• in the open field, mutants show an increase in total distance traveled indicating hyperactivity (J:207141)
• however anxiety-like behavior is not observed and mice show normal sociability and preference for social novelty (J:207141)
• mutants treated with Dox to turn off transgene expression from conception to 3 months of age show normal activity (J:207141)
• Dox administration from 1 to 3 months of age to turn off transgene expression before the onset of abnormalities is seen does not prevent abnormal phenotypes, with mutants developing hyperactivity (J:207141)
• in the open field, mutants show an increase in total distance traveled indicating hyperactivity (J:207141)
• however anxiety-like behavior is not observed and mice show normal sociability and preference for social novelty (J:207141)
• mutants treated with Dox to turn off transgene expression from conception to 3 months of age show normal activity (J:207141)
• Dox administration from 1 to 3 months of age to turn off transgene expression before the onset of abnormalities is seen does not prevent abnormal phenotypes, with mutants developing hyperactivity (J:207141)
• lower percentage of vocalization, with mutants showing 8% vocalization compared to 29% in wild-type mice (J:207141)
• lower percentage of vocalization, with mutants showing 8% vocalization compared to 29% in wild-type mice (J:207141)

adipose tissue
• mutants show lower abdominal fat weight (J:207141)
• mutants treated with Dox to turn off transgene expression from conception to 3 months of age show normal abdominal fat weight (J:207141)
• mutants show lower abdominal fat weight (J:207141)
• mutants treated with Dox to turn off transgene expression from conception to 3 months of age show normal abdominal fat weight (J:207141)

Mouse Models of Human Disease
OMIM ID Ref(s)
Potocki-Lupski Syndrome; PTLS 610883 J:207141




Genotype
MGI:5491208
cx51
Allelic
Composition
Tg(Camk2a-tTA)1Mmay/0
Tg(tetO-LMNB1)AF1Yfu/0
Genetic
Background
involves: FVB
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tg(Camk2a-tTA)1Mmay mutation (6 available)
Tg(tetO-LMNB1)AF1Yfu mutation (1 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
behavior/neurological
N
• normal motor behavior (J:197168)
• normal motor behavior (J:197168)




Genotype
MGI:5511058
cx52
Allelic
Composition
Tg(Camk2a-tTA)1Mmay/0
Tg(tetO-MAPT*P301L)#Kha/0
Genetic
Background
involves: FVB/N
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tg(Camk2a-tTA)1Mmay mutation (6 available)
Tg(tetO-MAPT*P301L)#Kha mutation (2 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
behavior/neurological
• reduction in exploration in open-field tests (J:102973)
• reduction in exploration in open-field tests (J:102973)
• mutants first exhibit impaired spatial reference memory at 2.5 months of age, showing a slightly reduced search bias for the target quadrant than controls in the Morris water maze (J:102973)
• spatial memory retention becomes more impaired with age, especially after 4 months of age, with the mean probe performance being equal to random swimming, indicating little or no retention of spatial memory (J:102973)
• mutants exhibit cognitive impairments in the acquisition phases of the Morris water maze, showing a longer mean distance to locate the hidden platform (J:102973)
• mutants first exhibit impaired spatial reference memory at 2.5 months of age, showing a slightly reduced search bias for the target quadrant than controls in the Morris water maze (J:102973)
• spatial memory retention becomes more impaired with age, especially after 4 months of age, with the mean probe performance being equal to random swimming, indicating little or no retention of spatial memory (J:102973)
• mutants exhibit cognitive impairments in the acquisition phases of the Morris water maze, showing a longer mean distance to locate the hidden platform (J:102973)
• clasping and limb retraction when lifted by the tail (J:102973)
• clasping and limb retraction when lifted by the tail (J:102973)
• mutants exhibit longer latencies to traverse a beam (J:102973)
• mutants exhibit longer latencies to traverse a beam (J:102973)
• mutants develop an age-dependent increase in the time taken to start swimming, however they are able to achieve comparable mean swim speeds during probe trials (J:102973)
• mutants develop an age-dependent increase in the time taken to start swimming, however they are able to achieve comparable mean swim speeds during probe trials (J:102973)
• from about 9.5 months of age, the most severely affected mutants develop hunched posture with hindlimb dysfunction and tail rigor (J:102973)
• from about 9.5 months of age, the most severely affected mutants develop hunched posture with hindlimb dysfunction and tail rigor (J:102973)
• develop dystonic posture with tail rigor at 9.5 months of age (J:102973)
• develop dystonic posture with tail rigor at 9.5 months of age (J:102973)
• from about 9.5 months of age, the most severely affected mutants exhibit decreased ambulation (J:102973)
• from about 9.5 months of age, the most severely affected mutants exhibit decreased ambulation (J:102973)

growth/size/body
• from about 9.5 months of age, the most severely affected mutants exhibit decreased body weight (J:102973)
• from about 9.5 months of age, the most severely affected mutants exhibit decreased body weight (J:102973)

nervous system
• 4-7% reduction in brain weight at 4 months of age (J:102973)
• 4-7% reduction in brain weight at 4 months of age (J:102973)
• atrophy of the forebrain is seen by 5 months of age (J:102973)
• atrophy of the forebrain is seen by 5 months of age (J:102973)
• age-dependent progression of tau processing that results in pathophysiological deposition of tau as mature tangles in the brain (J:102973)
• mutants exhibit age-dependent progression of neurofibrillary tangle formation, with tangles first appearing in the neocortex and then progressing into the hippocampus and limbic structures with increasing age (J:102973)
• neurofibrillary tangles develop in the hippocampus in a distinct pattern; mature tangles occur initially in CA1 pyramidal neurons, spread to CA2, and by 8.5 months of age include pyramidal neurons in CA2 and granular neurons of the dentate gyrus (J:102973)
• age-dependent progression of tau processing that results in pathophysiological deposition of tau as mature tangles in the brain (J:102973)
• mutants exhibit age-dependent progression of neurofibrillary tangle formation, with tangles first appearing in the neocortex and then progressing into the hippocampus and limbic structures with increasing age (J:102973)
• neurofibrillary tangles develop in the hippocampus in a distinct pattern; mature tangles occur initially in CA1 pyramidal neurons, spread to CA2, and by 8.5 months of age include pyramidal neurons in CA2 and granular neurons of the dentate gyrus (J:102973)
• abnormal conformations of tau are present in the hippocampus and neocortex of 2.5-month old mutants (J:102973)
• abnormal conformations of tau are present in the hippocampus and neocortex of 2.5-month old mutants (J:102973)
• reactive astrocytes in forebrains of 10 month old mutants (J:102973)
• reactive astrocytes in forebrains of 10 month old mutants (J:102973)
• atrophy of the dorsal corticospinal tracts accompanied by loss of neurofilament (J:102973)
• atrophy of the dorsal corticospinal tracts accompanied by loss of neurofilament (J:102973)
• degeneration in the hippocampus and neocortex is seen in 10 month old mutants (J:102973)
• degeneration in the hippocampus and neocortex is seen in 10 month old mutants (J:102973)
• massive neuronal loss, most apparent in the CA1 region of the hippocampus (J:102973)
• massive neuronal loss, most apparent in the CA1 region of the hippocampus (J:102973)
• spinal cords appear thinner, however, no decrease in motor neuron density is seen (J:102973)
• spinal cords appear thinner, however, no decrease in motor neuron density is seen (J:102973)

muscle
• develop dystonic posture with tail rigor at 9.5 months of age (J:102973)
• develop dystonic posture with tail rigor at 9.5 months of age (J:102973)

Mouse Models of Human Disease
OMIM ID Ref(s)
Alzheimer Disease; AD 104300 J:102973
Frontotemporal Dementia; FTD 600274 J:102973




Genotype
MGI:4414670
cx53
Allelic
Composition
Tg(Camk2a-tTA)1Mmay/0
Tg(tetO-LRRK2)1Cai/0
Genetic
Background
Not Specified
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tg(Camk2a-tTA)1Mmay mutation (6 available)
Tg(tetO-LRRK2)1Cai mutation (0 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
nervous system
N
• neuronal processes are normal (J:154755)
• neuronal processes are normal (J:154755)




Genotype
MGI:4414669
cx54
Allelic
Composition
Tg(Camk2a-tTA)1Mmay/0
Tg(tetO-LRRK2*G2019S)1Cai/0
Genetic
Background
Not Specified
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tg(Camk2a-tTA)1Mmay mutation (6 available)
Tg(tetO-LRRK2*G2019S)1Cai mutation (0 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
nervous system
• total neurite length is shortened compared to in wild-type mice (J:154755)
• neurons produce fewer neurites than in wild-type mice (J:154755)
• however, doxycyclin or forskolin treatment rescues the inhibited neurite growth (J:154755)
• total neurite length is shortened compared to in wild-type mice (J:154755)
• neurons produce fewer neurites than in wild-type mice (J:154755)
• however, doxycyclin or forskolin treatment rescues the inhibited neurite growth (J:154755)
• the longest process corresponding to the axon is reduced in length compared to in wild-type mice (J:154755)
• the longest process corresponding to the axon is reduced in length compared to in wild-type mice (J:154755)




Genotype
MGI:5438789
tg55
Allelic
Composition
Tg(Camk2a-tTA)1Mmay/0
Genetic
Background
(B6.Cg-Tg(Camk2a-tTA)1Mmay x 129X1/SvJ)F1
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tg(Camk2a-tTA)1Mmay mutation (6 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
behavior/neurological
• Background Sensitivity: freezing in response to unsignaled foot shock decreases in mutant and increases in control during final minutes of 5 minute test (J:185792)
• Background Sensitivity: freezing in response to unsignaled foot shock decreases in mutant and increases in control during final minutes of 5 minute test (J:185792)

nervous system
• Background Sensitivity: width of granule cell layer is 27% thinner than controls and the C57BL/6 congenic background (J:185792)
• Background Sensitivity: width of granule cell layer is 27% thinner than controls and the C57BL/6 congenic background (J:185792)
• Background Sensitivity: width of granule cell layer is 27% thinner than controls and the C57BL/6 congenic background (J:185792)
• Background Sensitivity: width of granule cell layer is 27% thinner than controls and the C57BL/6 congenic background (J:185792)




Genotype
MGI:5438785
tg56
Allelic
Composition
Tg(Camk2a-tTA)1Mmay/0
Genetic
Background
(B6.Cg-Tg(Camk2a-tTA)1Mmay x C3H/HeJ)F1
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tg(Camk2a-tTA)1Mmay mutation (6 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
nervous system
• Background Sensitivity: width of granule cell layer is 14% thinner than controls and the C57BL/6 congenic background (J:185792)
• Background Sensitivity: width of granule cell layer is 14% thinner than controls and the C57BL/6 congenic background (J:185792)
• Background Sensitivity: width of granule cell layer is 14% thinner than controls and the C57BL/6 congenic background (J:185792)
• Background Sensitivity: width of granule cell layer is 14% thinner than controls and the C57BL/6 congenic background (J:185792)




Genotype
MGI:5438807
tg57
Allelic
Composition
Tg(Camk2a-tTA)1Mmay/0
Genetic
Background
(B6.Cg-Tg(Camk2a-tTA)1Mmay x C3H/HeJ)F1 x C3H/HeJ
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tg(Camk2a-tTA)1Mmay mutation (6 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
nervous system
• Background Sensitivity: width of granule cell layer is 29% thinner than controls and C57BL/6 congenic background (J:185792)
• Background Sensitivity: width of granule cell layer is 29% thinner than controls and C57BL/6 congenic background (J:185792)
• Background Sensitivity: width of granule cell layer is 29% thinner than controls and C57BL/6 congenic background (J:185792)
• Background Sensitivity: width of granule cell layer is 29% thinner than controls and C57BL/6 congenic background (J:185792)




Genotype
MGI:5438788
tg58
Allelic
Composition
Tg(Camk2a-tTA)1Mmay/0
Genetic
Background
(B6.Cg-Tg(Camk2a-tTA)1Mmay x CBA/J)F1
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tg(Camk2a-tTA)1Mmay mutation (6 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
nervous system
• Background Sensitivity: width of granule cell layer is 30% thinner than controls and the C57BL/6 congenic background (J:185792)
• Background Sensitivity: width of granule cell layer is 30% thinner than controls and the C57BL/6 congenic background (J:185792)
• Background Sensitivity: width of granule cell layer is 30% thinner than controls and the C57BL/6 congenic background (J:185792)
• Background Sensitivity: width of granule cell layer is 30% thinner than controls and the C57BL/6 congenic background (J:185792)




Genotype
MGI:5438790
tg59
Allelic
Composition
Tg(Camk2a-tTA)1Mmay/0
Genetic
Background
(B6.Cg-Tg(Camk2a-tTA)1Mmay x DBA/1J)F1
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tg(Camk2a-tTA)1Mmay mutation (6 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
nervous system
• Background Sensitivity: width of granule cell layer is 17% thinner than controls and the C57BL/6 congenic background (J:185792)
• Background Sensitivity: width of granule cell layer is 17% thinner than controls and the C57BL/6 congenic background (J:185792)
• Background Sensitivity: width of granule cell layer is 17% thinner than controls and the C57BL/6 congenic background (J:185792)
• Background Sensitivity: width of granule cell layer is 17% thinner than controls and the C57BL/6 congenic background (J:185792)




Genotype
MGI:5438792
tg60
Allelic
Composition
Tg(Camk2a-tTA)1Mmay/0
Genetic
Background
(B6.Cg-Tg(Camk2a-tTA)1Mmay x FVB/NJ)F1
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tg(Camk2a-tTA)1Mmay mutation (6 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
nervous system
• Background Sensitivity: width of dentate gyrus granule cell layer is 21% thinner than controls and the C57BL/6 congenic background (J:185792)
• however, doxycycline administered in the first 6 weeks of life protects against cell loss (J:185792)
• Background Sensitivity: width of dentate gyrus granule cell layer is 21% thinner than controls and the C57BL/6 congenic background (J:185792)
• however, doxycycline administered in the first 6 weeks of life protects against cell loss (J:185792)