Phenotypes associated with this allele

• Allele Symbol: Tg(Camk2a-tTA)1Mmay
• Allele Name: transgene insertion 1, Mark Mayford
• Allele ID: MGI:2179066
• Summary: 73 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cn1	Psmc1^tm1Maye/Psmc1^tm1Maye Tg(Camk2a-tTA)1Mmay/0 Tg(tetO-cre)1Lin/0	involves: 129 * C57BL/6 * CD-1	MGI:3809773
cn2	Gabrg2^tm2Spet/Gabrg2^+ Tg(Camk2a-tTA)1Mmay/0 Tg(tetO-cre)LC1Bjd/0	involves: 129S1/Sv * 129X1/SvJ * BALB/c * C57BL/6	MGI:5474679
cn3	Grin1^tm1Rsp/Grin1^tm1Rsp Tg(Camk2a-tTA)1Mmay/? Tg(tetO-cre)LC1Bjd/?	involves: 129S1/Sv * 129X1/SvJ * BALB/c * C57BL/6	MGI:3708939
cn4	Npy1r^tm1.1Ceva/Npy1r^tm1.1Ceva Tg(Camk2a-tTA)1Mmay/0 Tg(tetO-cre)LC1Bjd/0	involves: 129S1/Sv * 129X1/SvJ * BALB/c * C57BL/6 * SJL	MGI:5307910
cx5	Apba2^tm1Tsuz/Apba2^tm1Tsuz Tg(Camk2a-tTA)1Mmay/0 Tg(tetO-APBA2,-lacZ)1Ito/0	B6.Cg-Apba2^tm1Tsuz 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-MAPT)32Lms/0	B6.Cg-Tg(Camk2a-tTA)1Mmay Tg(tetO-MAPT)32Lms	MGI:5828492
cx9	Tg(Camk2a-tTA)1Mmay/0 Tg(tetO-MAPT*A152T)L1Lms/0	B6.Cg-Tg(Camk2a-tTA)1Mmay Tg(tetO-MAPT*A152T)L1Lms	MGI:5828490
cx10	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
cx11	Bace1^tm1Pcw/Bace1^+ Tg(Camk2a-tTA)1Mmay/0 Tg(tetO-CDK5R1/GFP)337Lht/0	involves: 129S1/Sv * 129X1/SvJ * C57BL/6J	MGI:5634918
cx12	Tg(Camk2a-tTA)1Mmay/? Tg(tetO-DRD2)2-5Kndl/?	involves: 129S6/SvEvTac * C57BL/6 * CBA	MGI:5693761
cx13	Tg(Camk2a-tTA)1Mmay/0 Tg(tetO-Comt)1Kndl/0	involves: 129S6/SvEvTac * C57BL/6J	MGI:5694075
cx14	Tg(Camk2a-tTA)1Mmay/0 Fgf14^Tg(tetO-MAPT*P301L)4510Kha/Fgf14^+	involves: 129S6/SvEvTac * FVB/N	MGI:5558945
cx15	Tg(Camk2a-tTA)1Mmay/0 Tg(tetO/Prnp-APP*Swe*Lon)9191Krz/0	involves: 129S6/SvEvTac * FVB/N	MGI:5803810
cx16	Tg(Camk2a-tTA)1Mmay/? Fgf14^Tg(tetO-MAPT*P301L)4510Kha/?	involves: 129S6/SvEvTac * FVB/N	MGI:4819951
cx17	Tg(Camk2a-tTA)1Mmay/0 Tg(tetO-Csnk1d)#Mfla/0	involves: 129/Sv * C57BL/6	MGI:4452245
cx18	Tg(Camk2a-tTA)1Mmay/0 Fgf14^Tg(tetO-MAPT*P301L)4510Kha/Fgf14^+	involves: 129/Sv * C57BL/6 * CBA * FVB/N	MGI:5438795
cx19	Lrrk2^tm1.1Cai/Lrrk2^tm1.1Cai Tg(Camk2a-tTA)1Mmay/0 Tg(tetO-SNCA*A53T)E2Cai/0	involves: 129X1/SvJ * C57BL/6	MGI:4421016
cx20	Lrrk2^tm1.1Cai/Lrrk2^+ Tg(Camk2a-tTA)1Mmay/0 Tg(tetO-SNCA*A53T)E2Cai/0	involves: 129X1/SvJ * C57BL/6	MGI:4421006
cx21	Tg(Camk2a-tTA)1Mmay/0 Tg(tetO-SNCA)7Vle/0	involves: C3H/HeH * C57BL/6	MGI:5289970
cx22	Tg(Camk2a-tTA)1Mmay/0 Tg(tetO-SNCA*A53T)33Vle/0	involves: C3H/HeH * C57BL/6	MGI:5289971
cx23	Tg(Camk2a-tTA)1Mmay/0 Tg(tetO-APPSwInd)885Dbo/0 Tg(tetO-LRRK2*G2019S)E3Cai/0	involves: C3H/HeJ * C57BL/6	MGI:4421004
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-APPSwInd)102Dbo/0	involves: C3H/HeJ * C57BL/6 * CBA	MGI:3709182
cx26	Tg(Camk2a-tTA)1Mmay/0 Tg(tetO-APPSwInd)107Dbo/0	involves: C3H/HeJ * C57BL/6 * CBA	MGI:3709152
cx27	Tg(Camk2a-tTA)1Mmay/0 Tg(tetO-APPSwInd)18Dbo/0	involves: C3H/HeJ * C57BL/6 * CBA	MGI:3709154
cx28	Tg(Camk2a-tTA)1Mmay/0 Tg(tetO-TARDBP)12Vle/0	involves: C3H/HeJ * C57BL/6J	MGI:5448852
cx29	Tg(Camk2a-tTA)1Mmay/0 Tg(tetO-TARDBP*)4Vle/0	involves: C3H/HeJ * C57BL/6J	MGI:5448853
cx30	Tg(Camk2a-tTA)1Mmay/0 Tg(tetO-APPSwInd)Dbo/0	involves: C3H/HeJ * C57BL/6J	MGI:5812135
cx31	Tg(Camk2a-tTA)1Mmay/0 Tg(tetO/Prnp-TARDBP*)2Vle/0	involves: C3H/HeJ * C57BL/6J	MGI:5795743
cx32	Tg(Camk2a-tTA)1Mmay/0 Tg(tetO-MAPT*K280*I277P*I308P,-luc)#Eman/0	involves: C57BL/6	MGI:5554195
cx33	Tg(Camk2a-tTA)1Mmay/0 Tg(tetO-COX8A/EYFP)1Ksn/0	involves: C57BL/6	MGI:3700230
cx34	Tg(Camk2a-tTA)1Mmay/0 Tg(tetO-S100a10)1Pggd/0	involves: C57BL/6	MGI:3776630
cx35	Tg(Camk2a-tTA)1Mmay/0 Tg(tetO-LRRK2)C77Cai/0	involves: C57BL/6	MGI:4420995
cx36	Tg(Camk2a-tTA)1Mmay/0 Tg(tetO-LRRK2)C77Cai/0 Tg(tetO-SNCA*A53T)E2Cai/0	involves: C57BL/6	MGI:4420996
cx37	Tg(Camk2a-tTA)1Mmay/0 Tg(tetO-LRRK2*)D10Cai/0	involves: C57BL/6	MGI:4420997
cx38	Tg(Camk2a-tTA)1Mmay/0 Tg(tetO-LRRK2*)D10Cai/0 Tg(tetO-SNCA*A53T)E2Cai/0	involves: C57BL/6	MGI:4420998
cx39	Tg(Camk2a-tTA)1Mmay/0 Tg(tetO-LRRK2*G2019S)E3Cai/0	involves: C57BL/6	MGI:4420999
cx40	Tg(Camk2a-tTA)1Mmay/0 Tg(tetO-LRRK2*G2019S)E3Cai/0 Tg(tetO-SNCA*A53T)E2Cai/0	involves: C57BL/6	MGI:4421000
cx41	Tg(Camk2a-tTA)1Mmay/0 Tg(tetO-LRRK2)C7874Cai/0	involves: C57BL/6	MGI:4421001
cx42	Tg(Camk2a-tTA)1Mmay/0 Tg(tetO-LRRK2)C7874Cai/0 Tg(tetO-SNCA*A53T)E2Cai/0	involves: C57BL/6	MGI:4421002
cx43	Tg(Camk2a-tTA)1Mmay/0 Tg(tetO-SNCA*A53T)E2Cai/0	involves: C57BL/6	MGI:4421003
cx44	Tg(Camk2a-tTA)1Mmay/0 Tg(tetO-LRRK2*G2019S)E3Cai/0 Tg(tetO-SNCA)1Cai/0	involves: C57BL/6	MGI:4421005
cx45	Tg(Camk2a-tTA)1Mmay/0 Tg(tetO-SNCA)1Cai/0	involves: C57BL/6	MGI:4421057
cx46	Tg(Camk2a-tTA)1Mmay/0 Tg(tetO-SNCA)0Olri/0	involves: C57BL/6	MGI:5512702
cx47	Tg(Camk2a-tTA)1Mmay/0 Tg(tetO-MAPT*K280,-luc)#Eman/0	involves: C57BL/6	MGI:5554193
cx48	Tg(Camk2a-tTA)1Mmay/0 Tg(tetO-CHMP2B*)3Fbga/0	involves: C57BL/6	MGI:6278310
cx49	Tg(Camk2a-tTA)1Mmay/0 Tg(PDGFB-APPSwInd)J9Lms/0 Tg(tetO-MAPT*A152T)L1Lms/0	involves: C57BL/6 * C57BL/6J * DBA/2	MGI:5828495
cx50	Tg(Camk2a-tTA)1Mmay/0 Zbtb20^Tg(PDGFB-APPSwInd)20Lms/0 Tg(tetO-MAPT*A152T)L1Lms/0	involves: C57BL/6 * C57BL/6J * DBA/2	MGI:5828493
cx51	Tg(Camk2a-tTA)1Mmay/0 Zbtb20^Tg(PDGFB-APPSwInd)20Lms/0 Tg(tetO-MAPT)32Lms/0	involves: C57BL/6 * C57BL/6J * DBA/2	MGI:5828494
cx52	Tg(Camk2a-tTA)1Mmay/0 Tg(tetO-HTT*94Q,-lacZ)1Rhn/0	involves: C57BL/6 * CBA	MGI:3851446
cx53	Tg(Camk2a-tTA)1Mmay/0 Tg(tetO-DRD3)3-10Kndl/0	involves: C57BL/6 * CBA	MGI:5694057
cx54	Tg(Camk2a-tTA)1Mmay/0 Tg(tetO-DISC1*)1001Plet/0	involves: C57BL/6 * CBA * SJL	MGI:3838963
cx55	Tg(tetO-DISC1*)70Plet/0 Tg(Camk2a-tTA)1Mmay/0	involves: C57BL/6 * CBA * SJL	MGI:6287125
cx56	Tg(Camk2a-tTA)1Mmay/0 Tg(tetO-COX8A/PstI*)1Ctm/0	involves: C57BL/6 * CBA * SJL	MGI:5316005
cx57	Tg(Camk2a-tTA)1Mmay/0 Tg(tetO-Mtor*)#Atai/0	involves: C57BL/6 * DBA/2 * ICR	MGI:5634716
cx58	Tg(Camk2a-tTA)1Mmay/0 Tg(tetO-CDK5R1/GFP)337Lht/0	involves: C57BL/6J	MGI:3653709
cx59	Tg(Camk2a-tTA)1Mmay/0 Tg(tetO-Rai1,-EGFP)479Walz/0	involves: C57BL/6J * CBA/J	MGI:5555967
cx60	Tg(Camk2a-tTA)1Mmay/0 Tg(tetO-Rai1,-EGFP)463Walz/0	involves: C57BL/6J * CBA/J	MGI:5555966
cx61	Tg(Camk2a-tTA)1Mmay/0 Tg(tetO-LMNB1)AF1Yfu/0	involves: FVB	MGI:5491208
cx62	Tg(Camk2a-tTA)1Mmay/0 Fgf14^Tg(tetO-MAPT*P301L)4510Kha/Fgf14^+	involves: FVB/N	MGI:5511058
cx63	Tg(Camk2a-tTA)1Mmay/0 Tg(tetO-LRRK2)1Cai/0	Not Specified	MGI:4414670
cx64	Tg(Camk2a-tTA)1Mmay/0 Tg(tetO-LRRK2*G2019S)1Cai/0	Not Specified	MGI:4414669
tg65	Tg(Camk2a-tTA)1Mmay/0	129S6.Cg-Tg(Camk2a-tTA)1Mmay	MGI:5803805
tg66	Tg(Camk2a-tTA)1Mmay/0	(B6.Cg-Tg(Camk2a-tTA)1Mmay x 129X1/SvJ)F1	MGI:5438789
tg67	Tg(Camk2a-tTA)1Mmay/0	(B6.Cg-Tg(Camk2a-tTA)1Mmay x C3H/HeJ)F1	MGI:5438785
tg68	Tg(Camk2a-tTA)1Mmay/0	(B6.Cg-Tg(Camk2a-tTA)1Mmay x C3H/HeJ)F1 x C3H/HeJ	MGI:5438807
tg69	Tg(Camk2a-tTA)1Mmay/0	(B6.Cg-Tg(Camk2a-tTA)1Mmay x CBA/J)F1	MGI:5438788
tg70	Tg(Camk2a-tTA)1Mmay/0	(B6.Cg-Tg(Camk2a-tTA)1Mmay x DBA/1J)F1	MGI:5438790
tg71	Tg(Camk2a-tTA)1Mmay/0	(B6.Cg-Tg(Camk2a-tTA)1Mmay x FVB/NJ)F1	MGI:5438792
tg72	Tg(Camk2a-tTA)1Mmay/0	involves: C3H/HeJ * C57BL/6 * CBA	MGI:5438801
tg73	Tg(Camk2a-tTA)1Mmay/?	B6.Cg-Tg(Camk2a-tTA)1Mmay	MGI:5438794

Genotype
MGI:3809773

cn1

• Allelic Composition: Psmc1^tm1Maye/Psmc1^tm1Maye; Tg(Camk2a-tTA)1Mmay/0; Tg(tetO-cre)1Lin/0
• Genetic Background: involves: 129 * C57BL/6 * CD-1

• ♀: phenotype observed in females
• ♂: phenotype observed in males
• N: normal phenotype

mortality/aging

premature death ( J:138991 )

• die at 3-4 months of age

growth/size/body

postnatal growth retardation ( J:138991 )

• subtle growth retardation starting 5 weeks of age and becoming statistically significant by 8 weeks

behavior/neurological

abnormal spatial learning ( J:138991 )

• obvious spatial learning deficits in the Morris water maze at 8 weeks

abnormal eating behavior ( J:138991 )

• lack interest in locating food at 3-4 months of age

abnormal fear/anxiety-related behavior ( J:138991 )

• significantly more anxious in open-field analysis at 6 weeks

nervous system

increased neuron apoptosis ( J:138991 )

enlarged brain ventricles ( J:138991 )

• expansion of the ventricular cavities accompanying atrophy of the forebrain

loss of cortex neurons ( J:138991 )

• extensive neuronal loss by 8 weeks

thin cerebral cortex ( J:138991 )

forebrain atrophy ( J:138991 )

• significant progressive atrophy of the forebrain

gliosis ( J:138991 )

• extensive gliosis as a result of the neuronal damage

alpha-synuclein inclusion body ( J:138991 )

• numerous eosinophilic intraneuronal paranuclear inclusions, containing ubiquitin, alpha-synuclein, and p62, similar to Lewy bodies

neurodegeneration ( J:138991 )

• neurodegeneration was evident in neurons expressing Tg(Camk2a-tTA)1Mmay in forebrain, hippocampus, striatum, and amygdala

cellular

increased neuron apoptosis ( J:138991 )

Genotype
MGI:5474679

cn2

• Allelic Composition: Gabrg2^tm2Spet/Gabrg2⁺; Tg(Camk2a-tTA)1Mmay/0; Tg(tetO-cre)LC1Bjd/0
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * BALB/c * C57BL/6

behavior/neurological

increased susceptibility to pharmacologically induced seizures ( J:194736 )

• induced by pentylenetetrazil in mice treated with doxycycline treatment between conception and P21 or not treated with doxycycline at all

• induced by pentylenetetrazil compared with Gabrg2^tm2Spet heterozygotes

• doxycycline treatment between conception and P21 increased the time to first clonic seizure compared with mice not treated with doxycycline

• however, no seizure kindling effect is observed

nervous system

increased susceptibility to pharmacologically induced seizures ( J:194736 )

• induced by pentylenetetrazil in mice treated with doxycycline treatment between conception and P21 or not treated with doxycycline at all

• induced by pentylenetetrazil compared with Gabrg2^tm2Spet heterozygotes

• doxycycline treatment between conception and P21 increased the time to first clonic seizure compared with mice not treated with doxycycline

• however, no seizure kindling effect is observed

Genotype
MGI:3708939

cn3

• Allelic Composition: Grin1^tm1Rsp/Grin1^tm1Rsp; Tg(Camk2a-tTA)1Mmay/?; Tg(tetO-cre)LC1Bjd/?
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * BALB/c * C57BL/6

nervous system

abnormal long-term potentiation ( J:119834 )

• complete loss of NMDAR-mediated long term potential at dentate gyrus synapses

• however, long term potentiation at Schaffer collateral-CA1 synapses is similar to wild-type mice despite residual Cre activity in CA1 pyramidal cells

behavior/neurological

abnormal spatial working memory ( J:119834 )

• mice exhibit impaired spatial working memory but normal spatial reference memory in a 3 from 6 radial arm maze task

Genotype
MGI:5307910

cn4

• Allelic Composition: Npy1r^tm1.1Ceva/Npy1r^tm1.1Ceva; Tg(Camk2a-tTA)1Mmay/0; Tg(tetO-cre)LC1Bjd/0
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * BALB/c * C57BL/6 * SJL

adipose tissue

decreased subcutaneous adipose tissue amount ( J:180396 )

• Background Sensitivity: in doxycycline-treated mice raised by FVB/J

• however, doxycycline-treated mice raised by C57BL/6J dams exhibit normal white adipose tissue weight

decreased epididymal fat pad weight ( J:180396 )

• Background Sensitivity: in doxycycline-treated mice raised by FVB/J

• however, doxycycline-treated mice raised by C57BL/6J dams exhibit normal white adipose tissue weight

decreased total fat pad weight ( J:180396 )

• Background Sensitivity: visceral, epididymal and subcutaneous white adipose tissue in doxycycline-treated mice raised by FVB/J

• however, doxycycline-treated mice raised by C57BL/6J dams exhibit normal white adipose tissue weight

homeostasis/metabolism

increased circulating corticosterone level ( J:180396 )

• Background Sensitivity: in doxycycline-treated mice raised by FVB/J

• however, doxycycline-treated mice raised by C57BL/6J dams exhibit normal leptin levels

decreased circulating leptin level ( J:180396 )

• Background Sensitivity: in doxycycline-treated mice raised by FVB/J

• however, doxycycline-treated mice raised by C57BL/6J dams exhibit normal leptin levels

behavior/neurological

increased anxiety-related response ( 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

• however, doxycycline-treated mice fostered by C57BL/6J dams exhibit normal anxiety

decreased locomotor activity ( 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

growth/size/body

slow postnatal weight gain ( 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

integument

decreased subcutaneous adipose tissue amount ( J:180396 )

• Background Sensitivity: in doxycycline-treated mice raised by FVB/J

• however, doxycycline-treated mice raised by C57BL/6J dams exhibit normal white adipose tissue weight

Genotype
MGI:4418496

cx5

• Allelic Composition: Apba2^tm1Tsuz/Apba2^tm1Tsuz; Tg(Camk2a-tTA)1Mmay/0; Tg(tetO-APBA2,-lacZ)1Ito/0
• Genetic Background: B6.Cg-Apba2^tm1Tsuz Tg(Camk2a-tTA)1Mmay Tg(tetO-APBA2,-lacZ)1Ito

behavior/neurological

increased anxiety-related response ( J:148481 )

• with or without DOX administration, adult mice bury significantly more marbles than null mice in the marble burying test

• DOX administration to parental mice results in progeny which bury significantly fewer marbles than wild-type mice in the marble burying test

abnormal response to novel object ( J:148481 )

• without DOX administration mice displace significantly more food pellets from a tube than null mice in a burrowing test

decreased locomotor activity ( J:148481 )

• with or without DOX administration mice have decreased locomotor activity

abnormal social investigation ( 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

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

behavior/neurological

decreased anxiety-related response ( J:181086 )

• greater distance traveled and more exploration of the center in an open field test

• increased time spent in the open box in a light/dark box apparatus

• enter the open arm of an elevated plus maze more frequently than controls and travel greater distances in the apparatus

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

nervous system

enlarged lateral ventricles ( J:166114 )

• in mice never fed doxycycline or fed doxycycline only during development or only during adulthood

abnormal dorsal striatum morphology ( 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

abnormal ventral striatum morphology ( 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

enhanced long-term potentiation ( J:166114 )

• in mice never fed doxycycline but not mice fed doxycycline during adulthood only

decreased prepulse inhibition ( J:166114 )

• mice that never received doxycycline exhibit decreased prepulse inhibition compared with wild-type mice

• however, mice that receive doxycycline throughout development or only in adulthood or are treated with haloperidol exhibit normal prepulse inhibition

enhanced paired-pulse facilitation ( J:166114 )

• in mice never fed doxycycline but not mice fed doxycycline during adulthood only

behavior/neurological

behavior/neurological phenotype ( J:166114 )

N • mice exhibit no change in anxiety-related behavior

impaired contextual conditioning 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

• 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

• however, mice fed doxycycline only during development or only after training through retrieval exhibit normal long-term memory for contextual fear

abnormal spatial learning ( 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

impaired spatial working memory ( 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

hyperactivity ( J:166114 )

• in mice never fed doxycycline or only fed doxycycline during adulthood but not during development only

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
schizophrenia		DOID:5419	OMIM:181500	J:166114

Genotype
MGI:5828492

cx8

• Allelic Composition: Tg(Camk2a-tTA)1Mmay/0; Tg(tetO-MAPT)32Lms/0
• Genetic Background: B6.Cg-Tg(Camk2a-tTA)1Mmay Tg(tetO-MAPT)32Lms

behavior/neurological

increased susceptibility to pharmacologically induced seizures ( J:233816 )

• in response to pentylenetetrazol (PTZ), spike counts increase faster and reach higher levels in mutants than in controls, indicating a lowered threshold for chemically induced seizures

growth/size/body

decreased body weight ( J:233816 )

• adults weigh slightly less than controls

nervous system

increased susceptibility to pharmacologically induced seizures ( J:233816 )

• in response to pentylenetetrazol (PTZ), spike counts increase faster and reach higher levels in mutants than in controls, indicating a lowered threshold for chemically induced seizures

abnormal brain morphology ( J:233816 )

• accumulation of misfolded, nonfilamentous soluble tau in neurons

• however, mice do not exhibit neuronal loss at 20-23 months of age

abnormal brain wave pattern ( J:233816 )

• EEGs in 4-9 month old mice indicated that at baseline, epileptiform spikes are less abundant than in controls

abnormal CNS synaptic transmission ( J:233816 )

• mossy fiber synapse between dentate granule cells and CA3 pyramidal neurons exhibits a steeper slope of the input/output curve when fEPSPs are induced, indicating increased synaptic transmission strength at 4-8 months of age, with further increase in strength at 20 months

decreased paired-pulse facilitation ( J:233816 )

• paired-pulse ratio is lower at 20 months, but not a 4-8 months, of age

• however, mossy fiber long-term potentiation is unchanged at old age

mortality/aging

mortality/aging ( J:233816 )

N • mice survive into old age

Genotype
MGI:5828490

cx9

• Allelic Composition: Tg(Camk2a-tTA)1Mmay/0; Tg(tetO-MAPT*A152T)L1Lms/0
• Genetic Background: B6.Cg-Tg(Camk2a-tTA)1Mmay Tg(tetO-MAPT*A152T)L1Lms

behavior/neurological

increased susceptibility to pharmacologically induced seizures ( J:233816 )

• in response to pentylenetetrazol (PTZ), spike counts increase faster and reach higher levels in mutants than in controls, indicating a lowered threshold for chemically induced seizures

impaired spatial learning ( J:233816 )

• mice show age-dependent impairments in learning and memory in the Morris water maze

• at 4-6 months of age, mutants learn the task more poorly than controls but show no memory retention deficits in a probe trial 24 hours after the last training trial

• at 7-9 and 11-14 months of age, mutants do not differ from controls in task acquisition and memory retention testsat 7-9 and 11-14 months of age, mutants do not differ from controls in task acquisition and memory retention tests

• at 17-19 months, mutants show impaired learning, taking longer to reach the original platform location in the probe trial, do not cross the target location more often than equivalent locations in nontarget quadrants

abnormal nest building behavior ( J:233816 )

• mice show impairments in nest building behavior at 10-14 months of age and old mice show a trend in the same direction

• however, mice show normal social interaction, normal exploratory behavior and no anxiety related behaviors

growth/size/body

decreased body weight ( J:233816 )

• adults weigh slightly less than controls

nervous system

increased susceptibility to pharmacologically induced seizures ( J:233816 )

• in response to pentylenetetrazol (PTZ), spike counts increase faster and reach higher levels in mutants than in controls, indicating a lowered threshold for chemically induced seizures

abnormal brain morphology ( J:233816 )

• cortical and hippocampal levels of human Tau fragments are lower than in mice expressing wild-type human MAPT

• accumulation of misfolded, nonfilamentous soluble tau in neurons

• however, dense neuronal tau inclusions are not seen in 8, 20, or 23 month old mutants

• mice treated with doxycycline for 2 months, starting at 6 months of age show suppression of tau accumulation in neurons

hippocampal neuron degeneration ( J:233816 )

• mice at 20-23 months of age, but not at 4-6 months of age, show neuronal loss in dentate gyrus and CA3 but not in CA1

astrocytosis ( J:233816 )

• astrocytosis in the brain by 4 months of age

• treatment with doxycycline for 2 months, starting at 6 months of age, reverses astocytosis

abnormal brain wave pattern ( J:233816 )

• EEGs in 4-9 month old mice indicated that at baseline, epileptiform spikes are more abundant than in controls

abnormal CNS synaptic transmission ( J:233816 )

• mossy fiber synapse between dentate granule cells and CA3 pyramidal neurons exhibits a steeper slope of the input/output curve when fEPSPs are induced, indicating increased synaptic transmission strength at 4-8 months of age, with further increase in strength at 20 months

decreased paired-pulse facilitation ( J:233816 )

• paired-pulse ratio is lower at 20 months, but not a 4-8 months, of age indicating reduced paired-pulse facilitation

• however, mossy fiber long-term potentiation is unchanged at old age

mortality/aging

mortality/aging ( J:233816 )

N • mice survive into old age

Genotype
MGI:5478560

cx10

• 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

behavior/neurological

behavior/neurological phenotype ( J:195259 )

♂N • bitransgenic (off-DOX) males perform like wild-type males in Plus water maze apparatus, swimming abilities, and latency to find platform

abnormal long-term spatial reference memory ( 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

♂ • bi-transgenic mice (on-DOX) perform similar to non-transgenic controls in RAWM

♂ • 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

impaired spatial working 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)

♂ • 12.5 month old bi-transgenic males (on-DOX) exhibit a preference for the new arm

♂ • 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

nervous system

amyloid beta deposits ( 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

♂ • a low level of mobile, water-extractable Abeta42 is present in bitransgenic males treated with DOX for up to 4 weeks

homeostasis/metabolism

amyloid beta deposits ( 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

♂ • a low level of mobile, water-extractable Abeta42 is present in bitransgenic males treated with DOX for up to 4 weeks

Genotype
MGI:5634918

cx11

• Allelic Composition: Bace1^tm1Pcw/Bace1⁺; Tg(Camk2a-tTA)1Mmay/0; Tg(tetO-CDK5R1/GFP)337Lht/0
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6J

nervous system

nervous system phenotype ( J:177847 )

N • mice with transgene expression induced by removal of doxycycline from the food 4-6 weeks postnatal exhibit decreased amyloid beta in the hippocampus

N • mice exhibit normal synaptic plasticity and long term potentiation (LTP) is fully restored following a 6-week induction

N • mice exhibit normal density of synaptophysin puncta in the stratum radiatum of the hippocampus, indicating restoration of synapse density, following a 6-week induction

decreased brain weight ( J:177847 )

• brain weight is reduced in 6-week induced mice

hippocampal neuron degeneration ( J:177847 )

• reduction in the number of NeuN-positive cells in hippocampal area CA1 in 6-week induced mice

astrocytosis ( J:177847 )

• reactive astrogliosis is seen in the cortex and hippocampus in 6-week induced mice

behavior/neurological

behavior/neurological phenotype ( J:177847 )

N • 6-week induced mice show improved associate learning in contextual fear conditioning and are indistinguishable from controls

Genotype
MGI:5693761

cx12

• Allelic Composition: Tg(Camk2a-tTA)1Mmay/?; Tg(tetO-DRD2)2-5Kndl/?
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6 * CBA

behavior/neurological

abnormal learning/memory/conditioning ( J:106982 )

• mice exhibit a behavioral flexibility deficit in bowl reversal test

• mice exhibit increased latency to choose between two odors in single discrimination reversal trials

abnormal spatial reference memory ( J:106982 )

• memory impairment is observed in the eight-arm radial win-shift delayed non-match to sample (DNMTS) maze

• impaired acquisition of task is observed in the DNMTS T-maze; controls reach preset criterion more quickly than transgenic mice

• performance deficit in the T maze exists in the presence or absence of doxycycline

homeostasis/metabolism

increased dopamine level ( J:106982 )

• increase in dopamine levels

• decrease in dopamine turnover as determined by DOPAC:DA and HVA:DA ratios

abnormal metabolism ( J:106982 )

• decrease in basal metabolic activity in the caudate putamen as measured by glucose uptake

• increase in activity in primary motor and somatosensory cortices

Genotype
MGI:5694075

cx13

• Allelic Composition: Tg(Camk2a-tTA)1Mmay/0; Tg(tetO-Comt)1Kndl/0
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6J

behavior/neurological

abnormal 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

abnormal associative learning ( J:225566 )

♂ • slower learning in stimulus-response (conditional associative learning-CAL), although mice attain same performance level after training

♂ • 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

abnormal temporal memory ( 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

abnormal impulsive behavior control ( 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

nervous system

abnormal synaptic dopamine release ( J:225566 )

♂ • increase in dopamine release capacity in the dorsomedial striatum following stimulation of the medial forebrain bundle in comparison to controls

♂ • higher average peak dopamine current

♂ • increased total release volume

Genotype
MGI:5558945

cx14

• Allelic Composition: Tg(Camk2a-tTA)1Mmay/0; Fgf14^{Tg(tetO-MAPT*P301L)4510Kha}/Fgf14⁺
• Genetic Background: involves: 129S6/SvEvTac * FVB/N

behavior/neurological

impaired contextual conditioning behavior ( J:207366 )

• progressive decrease in percent of time spent freezing in response to unconditioned stimulus beginning at 2 months of age

impaired cued conditioning behavior ( J:207366 )

• progressive decrease in percent of time spent freezing in response to conditioned stimulus beginning at 6 months of age

increased exploration in new environment ( J:207366 )

abnormal anxiety-related response ( J:207366 )

decreased anxiety-related response ( 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

• 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

• exploration of light chamber is increased relative to nontransgenic mice at 6 months of age, but not 2 or 10 months

• higher ratio of time spent in light not dark relative to nontransgenic miceat 10 months of age, but not 2 or 6 months

increased anxiety-related response ( J:207366 )

• decreased tendency to explore the center of the open field relative to nontransgenic mice

increased locomotor activity ( J:207366 )

• mice exhibit progressive hyperactivity in open field analysis and elevated plus maze

• total distance travelled in open field assay is increased relative to nontransgenic mice at 6 and 10 months of age, but not 2 months

• average speed is increased relative to nontransgenic mice at 6 and 10 months of age, but not 2 months

• total time spent mobile is increased relative to nontransgenic mice at 6 and 10 months of age, but not 2 months

nervous system

neurofibrillary tangles ( 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

• 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

tau protein deposits ( J:207366 )

• tau burden increases with age in the amygdala and CA1 region of the hippocampus

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
frontotemporal dementia		DOID:9255	OMIM:600274	J:207366

Genotype
MGI:5803810

cx15

• Allelic Composition: Tg(Camk2a-tTA)1Mmay/0; Tg(tetO/Prnp-APP*Swe*Lon)9191Krz/0
• Genetic Background: involves: 129S6/SvEvTac * FVB/N

Age-related amyloid beta plaque progression in Tg(tetO/Prnp-APP*Swe*Lon)9191Krz/0 Tg(Camk2a-tTA)1Mmay/0 mice

growth/size/body

decreased body weight ( J:235351 )

• lower body weight in old mice

homeostasis/metabolism

amyloid beta deposits ( J:235351 )

• mice exhibit accumulation of amyloid beta plaques with age, first seen in the cerebral cortex at 8 months of age and then in the hippocampus between 10-12.5 months of age

• plaques include both dense-core and diffuse types and comparable plaque loads are seen in the cortex and hippocampus

• mice show an age-dependent increase in the production of amyloid beta 38, 40 and 42 in the brain, with more than 90% of amyloid beta 40 building the dense cores of plaques, and amyloid beta 42 being the main component of diffuse plaques and loosely core-associated oligomers

nervous system

amyloid beta deposits ( J:235351 )

• mice exhibit accumulation of amyloid beta plaques with age, first seen in the cerebral cortex at 8 months of age and then in the hippocampus between 10-12.5 months of age

• plaques include both dense-core and diffuse types and comparable plaque loads are seen in the cortex and hippocampus

• mice show an age-dependent increase in the production of amyloid beta 38, 40 and 42 in the brain, with more than 90% of amyloid beta 40 building the dense cores of plaques, and amyloid beta 42 being the main component of diffuse plaques and loosely core-associated oligomers

abnormal forebrain morphology ( J:235351 )

• mutants exhibit reduced forebrain weight compared to non-transgenic mice but similar in weight to single Tg(Camk2a-tTA)Mmay expressing mice

decreased dentate gyrus size ( J:235351 )

• mutants exhibit decreased dentate gyrus size compared to non-transgenic mice but size is similar to that seen in single Tg(Camk2a-tTA)Mmay expressing mice

gliosis ( J:235351 )

• gliosis is associated with dense-core plaques

abnormal axon morphology ( J:235351 )

• mice exhibit aggravated axonal curvature and swollen, dystrophic neurites surrounding plaques

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Alzheimer's disease		DOID:10652		J:235351

Genotype
MGI:4819951

cx16

• Allelic Composition: Tg(Camk2a-tTA)1Mmay/?; Fgf14^{Tg(tetO-MAPT*P301L)4510Kha}/?
• Genetic Background: involves: 129S6/SvEvTac * FVB/N

nervous system

decreased brain weight ( J:99626 )

• a significant loss in brain weight by 5.5 months

• when treated with doxycycline during 5.5 to 10 months, the loss of brain weight was significantly protected

abnormal hippocampus CA1 region morphology ( J:99626 )

• significant decrease in total numbers of CA1 hippocampal neurons

• CA1 neuron estimates were stabilized after brief (6- to 8-week) doxycycline treatment

forebrain atrophy ( J:99626 )

• gross atrophy of the forebrain was evident in a 10-month-old mouse

neurofibrillary tangles ( J:99626 )

• develop argyrophilic tangle-like inclusions in the cortex by 4 months and in the hippocampal formation by 5.5 months

• when treated with doxycycline at 2.5 month, the tau pathology ceased to progress

abnormal neuron morphology ( J:99626 )

• the neuronal inclusions composed of a mass of straight tau filaments

• when treated with doxycycline at 2.5 month, the tau pathology ceased to progress

decreased hippocampus pyramidal cell number ( J:99626 )

• approximately 23% of CA1 pyramidal cells remaining at 8.5 months

• CA1 neuron estimates were stabilized after brief (6- to 8-week) doxycycline treatment

behavior/neurological

abnormal spatial learning ( J:99626 )

• he retention of spatial memory examined by the Morris water maze were impaired as the mice aged

• deficit in spatial navigation was also seen in younger mice

• the performance improved when treated with doxycycline at 2.5 month-old or at 5.5 month-old

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Alzheimer's disease		DOID:10652		J:99626

Genotype
MGI:4452245

cx17

• Allelic Composition: Tg(Camk2a-tTA)1Mmay/0; Tg(tetO-Csnk1d)#Mfla/0
• Genetic Background: involves: 129/Sv * C57BL/6

behavior/neurological

behavior/neurological phenotype ( J:158611 )

N • mice exhibit normal social and circadian behaviors

abnormal behavioral response to xenobiotic ( J:158611 )

• mice exhibit a 40 minute delay in D-amphetamine-induced hyperlocomotion compared with similarly treated wild-type mice

• 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

decreased anxiety-related response ( J:158611 )

• in a dark-light choice test, mice exhibit increased rearing in the light compartment compared with wild-type mice

• in an elevated place maze, mice spend more time in the open arms than wild-type mice

• in a novelty suppressed feeding paradigm, mice exhibit shorter latency to feeding compared with wild-type mice

• however, mice exhibit normal anxiety-related behavior in an open field, forced swim, and tail suspension tests

abnormal locomotor activation ( J:158611 )

• mice exhibit a 40 minute delay in D-amphetamine-induced hyperlocomotion compared with similarly treated wild-type mice

• 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

increased vertical activity ( J:158611 )

• in an open field test, mice exhibit increased vertical activity compared with wild-type mice

• increased activity begins at 6 weeks of age and persists at least until 16 months of age

• however, treatment with methylphenidate or haloperidol suppresses vertical activity

increased locomotor activity ( J:158611 )

• in an open field test, mice exhibit increased horizontal and vertical activity compared with wild-type mice

• increased activity begins at 6 weeks of age and persists at least until 16 months of age

• however, treatment with methylphenidate or haloperidol decreases activity levels

abnormal nest building behavior ( J:158611 )

• in an open field box, mice fail to build a nest unlike wild-type mice

nervous system

abnormal striatum morphology ( J:158611 )

• protein expression of dopamine receptors 1 and 2 and NMDA receptors are decreased in the striatum compared to in wild-type mice

homeostasis/metabolism

increased physiological sensitivity to xenobiotic ( 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

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
attention deficit hyperactivity disorder		DOID:1094	OMIM:143465 OMIM:608903 OMIM:608904 OMIM:608905 OMIM:608906 OMIM:612311 OMIM:612312	J:158611

Genotype
MGI:5438795

cx18

• Allelic Composition: Tg(Camk2a-tTA)1Mmay/0; Fgf14^{Tg(tetO-MAPT*P301L)4510Kha}/Fgf14⁺
• Genetic Background: involves: 129/Sv * C57BL/6 * CBA * FVB/N

nervous system

abnormal dentate gyrus morphology ( J:185792 )

• progressive atrophy of dentate granule cells

hippocampal neuron degeneration ( J:185792 )

• progressive atrophy of hippocampal pyramidal neurons

Genotype
MGI:4421016

cx19

• Allelic Composition: Lrrk2^tm1.1Cai/Lrrk2^tm1.1Cai; Tg(Camk2a-tTA)1Mmay/0; Tg(tetO-SNCA*A53T)E2Cai/0
• Genetic Background: involves: 129X1/SvJ * C57BL/6

nervous system

nervous system phenotype ( J:156512 )

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

Genotype
MGI:4421006

cx20

• Allelic Composition: Lrrk2^tm1.1Cai/Lrrk2⁺; Tg(Camk2a-tTA)1Mmay/0; Tg(tetO-SNCA*A53T)E2Cai/0
• Genetic Background: involves: 129X1/SvJ * C57BL/6

nervous system

abnormal nervous system morphology ( J:156512 )

• somatic alpha synuclein in neurons is apparent at 12 months

microgliosis ( J:156512 )

• increased microglial activation is observed in the brain at 12 months

abnormal striatum morphology ( J:156512 )

• numbers of residual neurons is significantly lower than non transgenic controls

astrocytosis ( J:156512 )

• significant at 12 months

abnormal neuron morphology ( J:156512 )

• the Golgi complex shows severe fragmentation in 12 month old animals

neurodegeneration ( J:156512 )

• neurodegeneration significant at 12 months

immune system

microgliosis ( J:156512 )

• increased microglial activation is observed in the brain at 12 months

hematopoietic system

microgliosis ( J:156512 )

• increased microglial activation is observed in the brain at 12 months

Genotype
MGI:5289970

cx21

• Allelic Composition: Tg(Camk2a-tTA)1Mmay/0; Tg(tetO-SNCA)7Vle/0
• Genetic Background: involves: C3H/HeH * C57BL/6

nervous system

abnormal dentate gyrus morphology ( J:156801 )

• atrophy of hippocampal dentate gyrus neurons is seen by P21

alpha-synuclein inclusion body ( 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

behavior/neurological

behavior/neurological phenotype ( J:174555 )

N • mutants do not exhibit impaired contextual fear memory at 8 months of age

Genotype
MGI:5289971

cx22

• Allelic Composition: Tg(Camk2a-tTA)1Mmay/0; Tg(tetO-SNCA*A53T)33Vle/0
• Genetic Background: involves: C3H/HeH * C57BL/6

nervous system

increased neuron apoptosis ( J:156801 )

• dentate gyrus neuron loss is due to cell death not decreased cell proliferation

abnormal dentate gyrus morphology ( J:156801 , J:174555 )

• 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)

decreased hippocampus pyramidal cell number ( 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

thin cerebral cortex ( 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

gliosis ( J:156801 )

• gliosis in the hippocampus, near the dentate gyrus

astrocytosis ( 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

abnormal synaptic bouton morphology ( 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

alpha-synuclein inclusion body ( 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

• 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

• 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

neurodegeneration ( 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

hippocampal neuron degeneration ( J:156801 )

• postmitotic hippocampal dentate gyrus neuron degeneration is seen by P14, but no degeneration of proliferating cells

behavior/neurological

impaired contextual conditioning behavior ( 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

• normal chow-fed mutants at 12 months of age show impaired contextual fear memory

cellular

increased neuron apoptosis ( J:156801 )

• dentate gyrus neuron loss is due to cell death not decreased cell proliferation

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Lewy body dementia		DOID:12217	OMIM:127750	J:174555

Genotype
MGI:4421004

cx23

• 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

nervous system

neurodegeneration ( J:156512 )

• no acceleration of degeneration is observed compared to Tg(Camk2a-tTA)1Mmay/Tg(tetO-LRRK2*G2019S)E3Cai mice (G2019S)

Genotype
MGI:3696400

cx24

• Allelic Composition: Tg(Camk2a-tTA)1Mmay/0; Tg(tetO-APPSwInd)885Dbo/0
• Genetic Background: involves: C3H/HeJ * C57BL/6 * CBA

nervous system

amyloid beta deposits ( J:185792 )

abnormal dentate gyrus morphology ( J:185792 )

• mice exhibit a progressive neuronal atrophy that is most pronounced in the granule cell layer of hippocampal dentate gyrus

hippocampal neuron degeneration ( J:185792 )

• mice exhibit a progressive neuronal atrophy that is most pronounced in the granule cell layer of hippocampal dentate gyrus

• however, when mice are reared on doxycycline, cell loss is not observed

abnormal nervous system physiology ( J:109829 )

• mice produce transgenic APP protein at 10- to 30-fold over endogenous App levels

• expression of APPSw/Ind is higher relative to other three double transgenic lines, and suprression requires more doxycycline than the other three lines

homeostasis/metabolism

amyloid beta deposits ( J:185792 )

Genotype
MGI:3709182

cx25

• Allelic Composition: Tg(Camk2a-tTA)1Mmay/0; Tg(tetO-APPSwInd)102Dbo/0
• Genetic Background: involves: C3H/HeJ * C57BL/6 * CBA

nervous system

abnormal nervous system physiology ( J:109829 )

• mice produce transgenic APP protein at 10- to 30-fold over endogenous App levels

• suppression of transgene expression in these mice is most sensitive to doxycycline of the four lines tested

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Alzheimer's disease		DOID:10652		J:109829

Genotype
MGI:3709152

cx26

• Allelic Composition: Tg(Camk2a-tTA)1Mmay/0; Tg(tetO-APPSwInd)107Dbo/0
• Genetic Background: involves: C3H/HeJ * C57BL/6 * CBA

nervous system

amyloid beta deposits ( J:109829 )

• doxycycline-mediated suppression of transgenic APPSwInd synthesis leads to parallel reductions of amyloid beta peptide levels

• early onset amyloid formation is observed, with plaques observed as early as 8 weeks of age in mice receiving no doxycycline (DOX) treatment

• 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

• 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

• no lesions are observed in the cerebellum or brain stem

• animals receiving no treatment display moderate amyloid pathology at 6 months, which progresses to a severe amyloid burden by 9 months

• 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

abnormal dentate gyrus morphology ( J:185792 )

• mice exhibit a progressive neuronal atrophy that is most pronounced in the granule cell layer of hippocampal dentate gyrus

hippocampal neuron degeneration ( J:185792 )

• mice exhibit a progressive neuronal atrophy that is most pronounced in the granule cell layer of hippocampal dentate gyrus

• however, when mice are reared on doxycycline, cell loss is not observed

neurofibrillary tangles ( J:109829 )

• first visible plaques are fibrillary-cored deposits

abnormal astrocyte morphology ( J:109829 )

• activated astrocytes are found near plaques in all affected mice glial pathology is more severe in older mice

• if transgene expression is suppressed with doxycycline treatment, pathology does not progress in severity

abnormal nervous system physiology ( J:109829 )

• mice produce transgenic APP protein at 10- to 30-fold over endogenous App levels

• sensitivity of transgene suppression by doxycycline is intermediate between mice of line 885 and line 102

CNS inflammation ( J:109829 )

• neuritic pathology is observed around plaques; neuritic pathology is more severe in older mice

• if transgene expression is suppressed with doxycycline treatment, pathology does not progress in severity

behavior/neurological

abnormal locomotor activation ( J:109829 )

• hyperactive behavior is partially reversed in some mice by 1 month of transgene suppression starting at 4-5 months of age

increased locomotor activity ( J:109829 )

• untreated mice show hyperactivity, often running in circles around the perimeter of cages

• similar patterns of activity are observed in Morris water maze, with repetitive swim patterns seen in radial water maze swim test

• hyperactive phenotype penetrance is ~100%

• 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

abnormal circadian behavior ( J:109829 )

• all animals raised with doxycycline have altered circadian rhythms with less distinction between day- and nighttime activity levels

immune system

CNS inflammation ( J:109829 )

• neuritic pathology is observed around plaques; neuritic pathology is more severe in older mice

• if transgene expression is suppressed with doxycycline treatment, pathology does not progress in severity

homeostasis/metabolism

amyloid beta deposits ( J:109829 )

• doxycycline-mediated suppression of transgenic APPSwInd synthesis leads to parallel reductions of amyloid beta peptide levels

• early onset amyloid formation is observed, with plaques observed as early as 8 weeks of age in mice receiving no doxycycline (DOX) treatment

• 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

• 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

• no lesions are observed in the cerebellum or brain stem

• animals receiving no treatment display moderate amyloid pathology at 6 months, which progresses to a severe amyloid burden by 9 months

• 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

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Alzheimer's disease		DOID:10652		J:109829

Genotype
MGI:3709154

cx27

• Allelic Composition: Tg(Camk2a-tTA)1Mmay/0; Tg(tetO-APPSwInd)18Dbo/0
• Genetic Background: involves: C3H/HeJ * C57BL/6 * CBA

nervous system

amyloid beta deposits ( J:109829 )

• amyloid burden worsens in untreated animals between 6 and 9 months of age

• 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

abnormal nervous system physiology ( J:109829 )

• mice produce transgenic APP protein at 10- to 30-fold over endogenous App levels

• sensitivity of transgene suppression by doxycycline is intermediate between mice of line 885 and line 102

homeostasis/metabolism

amyloid beta deposits ( J:109829 )

• amyloid burden worsens in untreated animals between 6 and 9 months of age

• 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

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Alzheimer's disease		DOID:10652		J:109829

Genotype
MGI:5448852

cx28

• Allelic Composition: Tg(Camk2a-tTA)1Mmay/0; Tg(tetO-TARDBP)12Vle/0
• Genetic Background: involves: C3H/HeJ * C57BL/6J

nervous system

microgliosis ( J:170756 )

• microglial activation is seen in the cortex and hippocampus as early as 1 month after Dox removal

decreased brain weight ( J:170756 )

• 6 months following Dox removal

abnormal dentate gyrus morphology ( J:170756 )

• 20% loss of dentate gyrus neurons at 1 month and about 75% loss by 3 months after Dox removal

astrocytosis ( J:170756 )

• astrocytic activation is seen in the cortex and hippocampus as early as 1 month after Dox removal

neurodegeneration ( 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

behavior/neurological

limb grasping ( J:170756 )

• variable clasping behavior is seen approximately 1-3 months after Dox removal

hematopoietic system

microgliosis ( J:170756 )

• microglial activation is seen in the cortex and hippocampus as early as 1 month after Dox removal

immune system

microgliosis ( J:170756 )

• microglial activation is seen in the cortex and hippocampus as early as 1 month after Dox removal

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
amyotrophic lateral sclerosis type 10		DOID:0060201	OMIM:612069	J:170756

Genotype
MGI:5448853

cx29

• Allelic Composition: Tg(Camk2a-tTA)1Mmay/0; Tg(tetO-TARDBP*)4Vle/0
• Genetic Background: involves: C3H/HeJ * C57BL/6J

nervous system

abnormal dentate gyrus morphology ( J:170756 )

• about 50% loss of dentate gyrus neurons at 1 month after Dox removal

gliosis ( J:170756 )

• massive gliosis in cortical and hippocampal regions following Dox removal

• gliosis in the corticospinal tract, including the striatum, cerebral peduncles, medullary pyramids, and cervical spinal cord, following Dox removal

abnormal corticospinal tract morphology ( J:170756 )

• selective loss of corticospinal tract axons in cervical spinal cord associated with gliosis following Dox removal

• however, lower motor neuron loss is not observed

abnormal neuron morphology ( J:170756 )

• mutants rarely show accumulation of hyperphosphorylated, ubiquitinated cytoplasmic aggregates of TARDBP in neurons following Dox removal (around 1% of neurons showing aggregates)

neurodegeneration ( 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

• selective loss of corticospinal tract axons in cervical spinal cord following Dox removal

behavior/neurological

limb grasping ( J:170756 )

• abnormal limb clasping as early as 1 week after dox removal that continues throughout life until sacrifice

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
amyotrophic lateral sclerosis type 10		DOID:0060201	OMIM:612069	J:170756

Genotype
MGI:5812135

cx30

• Allelic Composition: Tg(Camk2a-tTA)1Mmay/0; Tg(tetO-APPSwInd)Dbo/0
• Genetic Background: involves: C3H/HeJ * C57BL/6J

nervous system

microgliosis ( J:236737 )

• activated microglia encapsulate amyloid beta plaques

• increase in the density of microglia surrounding plaques

amyloid beta deposits ( J:236737 )

• mice show moderate and severe plaque burden at 6 and 11 months of age, respectively

• amyloid beta plaques displace neurons and axon initial segments such that axon initial segments frequently bend or take circuitous trajectories around, but seldom through, amyloid beta plaques

abnormal astrocyte morphology ( J:236737 )

• hypertrophic astrocytes are seen in the vicinity of plaques

abnormal axon initial segment morphology ( J:236737 )

• occasionally axon initial segments traverse or are at the edges of plaques; these axon initial segments are fragmented, shorter, and thinner than those further away from the plaque

• decrease in the number of axon initial segments at 6 and 11 months of age

axon degeneration ( J:236737 )

• brains with heavy plaque burden have axons with random orientations and many dystrophic, degenerating axons, including axonal torpedoes

hematopoietic system

microgliosis ( J:236737 )

• activated microglia encapsulate amyloid beta plaques

• increase in the density of microglia surrounding plaques

homeostasis/metabolism

amyloid beta deposits ( J:236737 )

• mice show moderate and severe plaque burden at 6 and 11 months of age, respectively

• amyloid beta plaques displace neurons and axon initial segments such that axon initial segments frequently bend or take circuitous trajectories around, but seldom through, amyloid beta plaques

immune system

microgliosis ( J:236737 )

• activated microglia encapsulate amyloid beta plaques

• increase in the density of microglia surrounding plaques

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Alzheimer's disease		DOID:10652		J:236737

Genotype
MGI:5795743

cx31

• Allelic Composition: Tg(Camk2a-tTA)1Mmay/0; Tg(tetO/Prnp-TARDBP*)2Vle/0
• Genetic Background: involves: C3H/HeJ * C57BL/6J

nervous system

hippocampal neuron degeneration ( J:226974 )

loss of hippocampal neurons ( J:226974 )

• loss is progressive resulting in an 80% decrease in neurons at 19 months

• number of dentate gyrus neurons is decreased in mice at 10, 16 and 19, but not at 5, months after Dox removal as compared to controls

• reintroduction of Dox clears Tardbp C-terminal fragments (CTF) from the brain and halts neuron loss

astrocytosis ( J:226974 )

• increase in GFAP reactivity 10 months after Dox removal

neuronal cytoplasmic inclusions ( J:226974 )

• accumulation of ubiquitin and mitochondrial proteins in distal dendrites of the stratum lacunosum moleculare (SLM) layer of the hippocampus 5 months after Dox withdrawal, reintroduction of Dox does not clear ubiquitin

• ubiquitin forms a discrete punctate pattern in SLM

Genotype
MGI:5554195

cx32

• Allelic Composition: Tg(Camk2a-tTA)1Mmay/0; Tg(tetO-MAPT*K280*I277P*I308P,-luc)#Eman/0
• Genetic Background: involves: C57BL/6

nervous system

nervous system phenotype ( J:131379 , J:169532 )

N • tau aggregates, neurofibrillary tangles, and neuron degeneration are not seen even after 22 months after doxycycline removal to induce gene expression (J:131379)

N (J:169532)

impaired synaptic plasticity ( J:169532 )

• decrease in synaptic facilitation in mice at 10 months after doxycycline removal which is reversed upon doxycycline treatment to switch off expression

• mice at 10 months after doxycycline removal show reduced extent of frequency facilitation

decreased post-tetanic potentiation ( 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

abnormal paired-pulse facilitation ( J:169532 )

• paired-pulse facilitation (PPF) is altered at the 10 and 20 ms interval in CA1 region of the hippocampus

Genotype
MGI:3700230

cx33

• Allelic Composition: Tg(Camk2a-tTA)1Mmay/0; Tg(tetO-COX8A/EYFP)1Ksn/0
• Genetic Background: involves: C57BL/6

normal phenotype

no abnormal phenotype detected ( J:118452 )

• mice appear normal and healthy, and expression of EYFP is detected in neuronal mitochondria under appropriate conditions

Genotype
MGI:3776630

cx34

• Allelic Composition: Tg(Camk2a-tTA)1Mmay/0; Tg(tetO-S100a10)1Pggd/0
• Genetic Background: involves: C57BL/6

behavior/neurological

abnormal depression-related behavior ( J:104116 )

• mice exhibit decreased depression-related behavior such as immobility when suspended by their tails

• however, treatment with doxycycline restores normal depression-related behaviors

decreased anxiety-related response ( J:104116 )

• mice exhibit decreased thigmotaxis and increased horizontal activity in an open-field test

• however, treatment with doxycycline restores normal anxiety-related behaviors

hyperactivity ( J:104116 )

Genotype
MGI:4420995

cx35

• Allelic Composition: Tg(Camk2a-tTA)1Mmay/0; Tg(tetO-LRRK2)C77Cai/0
• Genetic Background: involves: C57BL/6

nervous system

nervous system phenotype ( J:156512 )

N • no neuronal degeneration is observed at 1 month in the striatum or cortex of LRRK2WT-L mice

Genotype
MGI:4420996

cx36

• Allelic Composition: Tg(Camk2a-tTA)1Mmay/0; Tg(tetO-LRRK2)C77Cai/0; Tg(tetO-SNCA*A53T)E2Cai/0
• Genetic Background: involves: C57BL/6

nervous system

abnormal nervous system morphology ( 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

microgliosis ( J:156512 )

• increased microglial activation is observed in the brain

astrocytosis ( J:156512 )

• A53T/LRRK2WT-L mice show significant elevation of GFAP-positive astrocytes in the striatum compared to A53T mice

neurodegeneration ( J:156512 )

• neurodegeneration is accelerated in the striatum

abnormal nervous system physiology ( J:156512 )

• increasing accumulation of alpha-synuclein is detected in cell bodies at 1 month

behavior/neurological

abnormal locomotor behavior ( J:156512 )

• mice show no apparent motor phenotype up to 6 months of age

hematopoietic system

microgliosis ( J:156512 )

• increased microglial activation is observed in the brain

immune system

microgliosis ( J:156512 )

• increased microglial activation is observed in the brain

Genotype
MGI:4420997

cx37

• Allelic Composition: Tg(Camk2a-tTA)1Mmay/0; Tg(tetO-LRRK2*)D10Cai/0
• Genetic Background: involves: C57BL/6

nervous system

abnormal neuron morphology ( J:156512 )

• increased framentation of the Golgi complex is observed in KD mice

Genotype
MGI:4420998

cx38

• Allelic Composition: Tg(Camk2a-tTA)1Mmay/0; Tg(tetO-LRRK2*)D10Cai/0; Tg(tetO-SNCA*A53T)E2Cai/0
• Genetic Background: involves: C57BL/6

nervous system

abnormal nervous system morphology ( J:156512 )

• increasing accumulation of alpha-synuclein is detected in cell bodies at 1 month in A53T/KD mice compared to KD animals

abnormal neuron morphology ( J:156512 )

• increased framentation of the Golgi complex is observed

abnormal nervous system physiology ( J:156512 )

• neuropathology is accelerated in A53T/KD mice compared to A53T mice

Genotype
MGI:4420999

cx39

• Allelic Composition: Tg(Camk2a-tTA)1Mmay/0; Tg(tetO-LRRK2*G2019S)E3Cai/0
• Genetic Background: involves: C57BL/6

growth/size/body

decreased body weight ( 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

behavior/neurological

behavior/neurological phenotype ( J:156512 )

N • mice show normal performance in the rotarod test

hyperactivity ( 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

nervous system

nervous system phenotype ( J:156512 )

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

N • no increase in reactive astrocytosis or microglial activation are detected in the striatum or cortex at 20 months

N • no alpha-synuclein accumulation is observed in neurons at 20 months

abnormal neuron morphology ( J:156512 )

• the Golgi complex is drastically altered in neurons at 1 month, appearing thinner and fragmented

• at 6 months fragmentation of the cis-Golgi apparatus is similar to that in LRRK2WT and A53T/LRRK2 neurons

• at 1 month, the medial/trans-Golgi in neurons is significantly altered

abnormal nervous system physiology ( J:156512 )

• brain homogenates moderately elevated levels of ubiquitinated proteins at 18 months compared to non-transgenic controls

Genotype
MGI:4421000

cx40

• Allelic Composition: Tg(Camk2a-tTA)1Mmay/0; Tg(tetO-LRRK2*G2019S)E3Cai/0; Tg(tetO-SNCA*A53T)E2Cai/0
• Genetic Background: involves: C57BL/6

nervous system

abnormal nervous system morphology ( J:156512 )

• substantial accumulation of alpha-synuclein is detected in cell bodies at 1 month

microgliosis ( J:156512 )

• exacerbated in the striatum compared to A53T mice at 1 month of age

• levels of microglial activation are higher than in A53T/LRRK2WT mice

abnormal dorsal striatum morphology ( J:156512 )

astrocytosis ( J:156512 )

• exacerbated in the striatum compared to A53T mice at 1 month of age

• levels of GFAP-positive cells are higher than in A53T/LRRK2WT mice

abnormal neuron morphology ( J:156512 )

• the Golgi complex is drastically altered in neurons at 1 month with severely fragmented

• at 1 month, the medial/trans-Golgi in neurons is severely fragmented

abnormal neuron mitochondrial morphology ( 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

alpha-synuclein inclusion body ( 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

neurodegeneration ( J:156512 )

• exacerbated in the striatum compared to A53T mice at 1 month of age

• dramatic loss (>85%) of striatal neurons is seen in the dorsal striatum

hematopoietic system

microgliosis ( J:156512 )

• exacerbated in the striatum compared to A53T mice at 1 month of age

• levels of microglial activation are higher than in A53T/LRRK2WT mice

immune system

microgliosis ( J:156512 )

• exacerbated in the striatum compared to A53T mice at 1 month of age

• levels of microglial activation are higher than in A53T/LRRK2WT mice

cellular

abnormal neuron mitochondrial morphology ( 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

Genotype
MGI:4421001

cx41

• Allelic Composition: Tg(Camk2a-tTA)1Mmay/0; Tg(tetO-LRRK2)C7874Cai/0
• Genetic Background: involves: C57BL/6

nervous system

nervous system phenotype ( J:156512 )

N • no gross neuropathological phenotypes are observed in 12-month old animals

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

abnormal neuron morphology ( J:156512 )

• the Golgi complex is drastically altered in neurons at 1 month, appearing thinner and fragmented

• at 6 months fragmentation of the cis-Golgi apparatus is similar to that in LRRK2WT and A53T/LRRK2 neurons

• 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

Genotype
MGI:4421002

cx42

• Allelic Composition: Tg(Camk2a-tTA)1Mmay/0; Tg(tetO-LRRK2)C7874Cai/0; Tg(tetO-SNCA*A53T)E2Cai/0
• Genetic Background: involves: C57BL/6

nervous system

abnormal nervous system morphology ( J:156512 )

• increasing accumulation of alpha-synuclein is detected in cell bodies at 1 month compared to A53T/LRRK2WT-L animals

microgliosis ( J:156512 )

• increased microglial activation is observed in the brain

abnormal dorsal striatum morphology ( J:156512 )

• neuron loss is detected at 6 months and later

abnormal cerebral cortex morphology ( J:156512 )

astrocytosis ( J:156512 )

• A53T/LRRK2WT mice show significant elevation of GFAP-positive astrocytes in the striatum compared to A53T mice

• more GFAP-positive astrocytes are found in the brain than in A53T/LRRK2WT-L brains

abnormal neuron morphology ( J:156512 )

• the Golgi complex is drastically altered in neurons at 1 month with severely fragmented cis-Golgi

• at 1 month, the medial/trans-Golgi in neurons is severely fragmented

neurodegeneration ( J:156512 )

• neurodegeneration is accelerated in the striatum

• dramatic loss (>80%) of striatal neurons is seen in the dorsal striatum

• most degenerating neurons are striatal medium-sized spiny neurons (MSN)

abnormal nervous system physiology ( J:156512 )

• neuropathology is accelerated in mice compared to A53T mice

• 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

• brain homogenates contain significantly elevated levels of ubiquitinated proteins at 3 months

immune system

microgliosis ( J:156512 )

• increased microglial activation is observed in the brain

hematopoietic system

microgliosis ( J:156512 )

• increased microglial activation is observed in the brain

Genotype
MGI:4421003

cx43

• Allelic Composition: Tg(Camk2a-tTA)1Mmay/0; Tg(tetO-SNCA*A53T)E2Cai/0
• Genetic Background: involves: C57BL/6

growth/size/body

decreased body weight ( 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

behavior/neurological

abnormal locomotor activation ( J:156512 )

increased vertical activity ( J:156512 )

• mice display elevated rearing activities at 6 months of age

increased locomotor activity ( J:156512 )

• at 2 months of age, mice show drastically increased ambulatory activity

nervous system

abnormal nervous system morphology ( 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

• significant rescue of phenotype is observed when animals are treated with doxycycline to inhibit transgene expression

microgliosis ( J:156512 )

• significant at 12 months

• significant rescue of phenotype is observed when animals are treated with doxycycline to inhibit transgene expression

abnormal striatum morphology ( J:156512 )

• neuron loss is detected at 6 months and later

• significant rescue of phenotype is observed when animals are treated with doxycycline to inhibit transgene expression

abnormal cerebral cortex morphology ( J:156512 )

• neuron loss is detected at 6 months and later

• in 6 month old mice but not in nontransgenic controls, elevated levels of ubiquitin are detected in somas and nuclei of cortical neurons, but

astrocytosis ( J:156512 )

• significant at 12 months

• significant rescue of phenotype is observed when animals are treated with doxycycline to inhibit transgene expression

abnormal neuron morphology ( J:156512 )

• the Golgi complex is drastically altered in neurons at 1 month, appearing thinner and fragmented

• significant increase in Golgi fragmentation is observed at 6 months

• 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

• significant rescue of phenotype is observed when animals are treated with doxycycline to inhibit transgene expression

abnormal neuron mitochondrial morphology ( 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

alpha-synuclein inclusion body ( 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

• significant decrease in HMW alpha-synuclein in total brain homogenates is observed when animals are treated with doxycycline to inhibit transgene expression

neurodegeneration ( J:156512 )

• widespread degeneration is observed at 20 months

• age-dependent, progressive neurodegeneration occurs

• neuronal loss is detected in the frontal cortex (>80%) and dorsal striatum (>74%) at 20 months

• a significant reduction (>30%) of striatal neurons is seen at 6 months

abnormal nervous system physiology ( J:156512 )

• while 3-month old A53T mice show no abnormal neuropathology, but neuropathology is evident at 12 and 20 months

• 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

• brain homogenates contain significantly elevated levels of ubiquitinated proteins at 3 months

hematopoietic system

microgliosis ( J:156512 )

• significant at 12 months

• significant rescue of phenotype is observed when animals are treated with doxycycline to inhibit transgene expression

immune system

microgliosis ( J:156512 )

• significant at 12 months

• significant rescue of phenotype is observed when animals are treated with doxycycline to inhibit transgene expression

cellular

abnormal neuron mitochondrial morphology ( 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

Genotype
MGI:4421005

cx44

• Allelic Composition: Tg(Camk2a-tTA)1Mmay/0; Tg(tetO-LRRK2*G2019S)E3Cai/0; Tg(tetO-SNCA)1Cai/0
• Genetic Background: involves: C57BL/6

nervous system

abnormal nervous system morphology ( J:156512 )

• somatic alpha synuclein in neurons is apparent at 1 month

Genotype
MGI:4421057

cx45

• Allelic Composition: Tg(Camk2a-tTA)1Mmay/0; Tg(tetO-SNCA)1Cai/0
• Genetic Background: involves: C57BL/6

nervous system

nervous system phenotype ( J:156512 )

N • no alpha-synuclein accumulation is observed in neurons at 1 month

Genotype
MGI:5512702

cx46

• Allelic Composition: Tg(Camk2a-tTA)1Mmay/0; Tg(tetO-SNCA)0Olri/0
• Genetic Background: involves: C57BL/6

behavior/neurological

abnormal motor 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

abnormal long-term spatial reference memory ( J:132774 )

• 52 week old mutants show impaired memory retention in the Morris water maze when tested 7 days later for their platform preference

abnormal motor coordination/balance ( J:132774 )

• progressive impairment of motor performance that begins around 30 weeks of age

impaired coordination ( 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

• progressive motor decline is not reversed by treatment with doxycycline but it does halt further decline

nervous system

abnormal neuron differentiation ( 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

• doxycycline treatment to inhibit transgene expression starting at 16 weeks of age does not result in reduced neurogenesis

abnormal substantia nigra morphology ( J:132774 )

• dark cells in the substantia nigra and axonal pathology with condensed mitochondria and lipid droplets indicating degeneration of nigral cells

abnormal substantia nigra pars reticulata morphology ( J:132774 )

• large lipid-like drops are seen between nerve fibers of the pars reticulata

hippocampus pyramidal cell degeneration ( J:132774 )

• dark degenerated pyramidal cells are scattered between unaffected neurons

decreased dopaminergic neuron number ( J:132774 )

• reduction of dopaminergic neurons in the substantia nigra; degenerating cells are most prominent in the pars reticulata

abnormal synaptic bouton morphology ( J:132774 )

• reduction of dopamine trasnporter binding sites at presynaptic terminals

decreased neuronal precursor cell number ( J:132774 )

• total number of neuroblasts is reduced in the hippocampus

neuron degeneration ( 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

hippocampal neuron degeneration ( J:132774 )

• proximal dendrites of the CA3 neurons show signs of degeneration

• dark cell degeneration in the CA1 pyramidal cells as well as in interneurons and granule cells of the dentate gyrus

alpha-synuclein inclusion body ( J:132774 )

• many alpha-synuclein positive mossy fiber terminals, which may show swollen vesicles and enlarged mitochondria, form asymmetric contracts with immunonegative dendritic spines

• alpha-synuclein accumulates in the stratum lacunosum moleculare and in mossy fibers and their terminals

cellular

abnormal neuron differentiation ( 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

• doxycycline treatment to inhibit transgene expression starting at 16 weeks of age does not result in reduced neurogenesis

homeostasis/metabolism

decreased dopamine level ( J:132774 )

• reduction of dopamine level in the olfactory bulb in aged mice

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Parkinson's disease		DOID:14330	OMIM:PS168600	J:132774

Genotype
MGI:5554193

cx47

• Allelic Composition: Tg(Camk2a-tTA)1Mmay/0; Tg(tetO-MAPT*K280,-luc)#Eman/0
• Genetic Background: involves: C57BL/6

nervous system

neurofibrillary tangles ( J:131379 , J:169532 )

• 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 protein deposits ( J:131379 , J:169532 )

• 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)

astrocytosis ( J:131379 , J:169532 )

• 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)

abnormal neurite morphology ( J:131379 )

• by 15 months after doxycycline removal, dystrophic neurites are seen

abnormal synapse morphology ( J:131379 , J:169532 )

• 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)

neuron degeneration ( J:131379 , J:169532 )

• 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)

impaired synaptic plasticity ( J:169532 )

• mice at 10 months after doxycycline removal show reduced short term plasticity at the mossy fiber-CA3 synapse

• 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

• 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

reduced long-term potentiation ( 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

decreased post-tetanic potentiation ( 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

behavior/neurological

impaired passive avoidance behavior ( 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

impaired spatial learning ( 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

• however, mice show normal behavior in the probe trial after the acquisition phase

• 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

impaired coordination ( 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

• however, grip strength and performance in spontaneous home cage activity is normal at 10 months after doxycycline removal

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Alzheimer's disease		DOID:10652		J:131379 , J:169532

Genotype
MGI:6278310

cx48

• Allelic Composition: Tg(Camk2a-tTA)1Mmay/0; Tg(tetO-CHMP2B*)3Fbga/0
• Genetic Background: involves: C57BL/6

behavior/neurological

increased thigmotaxis ( J:227797 )

• mice show an age-dependent decrease in thigmotaxis in the elevated-plus-maze test at 4 and 8 months of age

• however, mice exhibit normal behavior in an object recognition task, normal locomotion, and normal olfactory discrimination

increased grooming behavior ( J:227797 )

• 7 of 36 aged mice (14-20 months) exhibit cutaneous lesions that indicate excessive grooming

abnormal social investigation ( J:227797 )

• in the resident-intruder test of social interaction, mice show decreased interaction times at the end of the test, but not at the beginning of the test

• in the three-chamber social paradigm, mice show a more pronounced, age-dependent decrease in sociability, particularly in trial 5, when both social partners are present

• treatment of 8 month old mice with a general AMPAR antagonist, NBQX, increases sociability

• however, treatment with the NMDA receptor antagonist AP5 has no effect on sociability

• mice injected with an adenovirus expressing miR-124 into the medial prefrontal cortex show an increase in sociability 1 month after injection

• mice injected into the medial prefrontal cortex with a lentiviral vector encoding shRNA directed against the AMPAR subunit Gria2 show partial rescue of social deficits

nervous system

abnormal cerebral cortex morphology ( J:227797 )

• 8 month old mice exhibit ubiquitin deposits and an increase of p62 in insoluble fraction in the cortex

• levels of microRNA miR-124 are decreased in the superficial layers of the cerebral cortex

abnormal cerebral cortex pyramidal cell morphology ( J:227797 )

• spine number and density of pyramidal neurons in the superficial layers (II and III) of the medial prefrontal cortex are increased in 8 month old mice; this increase is due to thin spines that are considered to be immature

• however, no spine changes are seen in hippocampal CA3 pyramidal neurons

astrocytosis ( J:227797 )

• 8 month old mice exhibit astrogliosis

increased dendritic spine density ( J:227797 )

• spine density of pyramidal neurons in the superficial layers of the medial prefrontal cortex are increased in 8 month old mice

abnormal CNS synaptic transmission ( J:227797 )

• synapses exhibit a lower rectification index for AMPAR-mediated excitatory postsynaptic currents (EPSCs) and evoked EPSCs of neurons are less sensitive to inhibition by Naspm, a specific inhibitor of calcium-permeable AMPARs, indicating altered AMPAR subunit composition that leads to an imbalance between calcium-permeable and calcium-impermeable AMPARs

• however, neither the amplitude or frequency of AMPAR-mediated miniature excitatory postsynaptic currents are altered

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
frontotemporal dementia		DOID:9255	OMIM:600274	J:227797

Genotype
MGI:5828495

cx49

• Allelic Composition: Tg(Camk2a-tTA)1Mmay/0; Tg(PDGFB-APPSwInd)J9Lms/0; Tg(tetO-MAPT*A152T)L1Lms/0
• Genetic Background: involves: C57BL/6 * C57BL/6J * DBA/2

mortality/aging

lethality, incomplete penetrance ( J:233816 )

• fewer than the expected numbers (8 of 282) of mice were obtained

• surviving mice do not die before adulthood, with one dying at 7 months, another at 10 months and the remaining being alive at 11-17 months

nervous system

abnormal brain wave pattern ( J:233816 )

• EEG recordings show more abundant epileptic spikes than in controls

Genotype
MGI:5828493

cx50

• Allelic Composition: Tg(Camk2a-tTA)1Mmay/0; Zbtb20^{Tg(PDGFB-APPSwInd)20Lms}/0; Tg(tetO-MAPT*A152T)L1Lms/0
• Genetic Background: involves: C57BL/6 * C57BL/6J * DBA/2

mortality/aging

lethality at weaning ( J:233816 )

• surviving mice die shortly after weaning

preweaning lethality, incomplete penetrance ( J:233816 )

• fewer than the expected numbers (only 2 of 141) of mice were obtained, indicating early lethality

Genotype
MGI:5828494

cx51

• Allelic Composition: Tg(Camk2a-tTA)1Mmay/0; Zbtb20^{Tg(PDGFB-APPSwInd)20Lms}/0; Tg(tetO-MAPT)32Lms/0
• Genetic Background: involves: C57BL/6 * C57BL/6J * DBA/2

mortality/aging

lethality, incomplete penetrance ( J:233816 )

• fewer than the expected numbers (only 5 of 94) of mice were obtained, indicating a trend toward early lethality

premature death ( J:233816 )

• 2 of 5 surviving mice die at 2 months of age

Genotype
MGI:3851446

cx52

• Allelic Composition: Tg(Camk2a-tTA)1Mmay/0; Tg(tetO-HTT*94Q,-lacZ)1Rhn/0
• Genetic Background: involves: C57BL/6 * CBA

mortality/aging

premature death ( J:61490 )

• some mice die between 8 to 10 months due to injuries sustain from fighting with other mice

prenatal lethality, incomplete penetrance ( J:61490 )

• fewer than expected mice are recovered due to prenatal lethality

• however, treatment of pregnant dams with doxycycline eliminates prenatal lethality

nervous system

decreased brain size ( J:61490 )

enlarged brain ventricles ( J:61490 )

• ventricles are enlarged compared to in wild-type mice

abnormal dorsal striatum morphology ( J:61490 )

• the area of the caudate putamen is reduced compared to in wild-type mice

• however, treatment with doxycycline after the onset of symptoms restores some of the caudate putamen area

decreased striatum size ( J:61490 )

• the striatum is reduced in size compared to in wild-type mice

• the ventricular zone of the striatum is narrower than in wild-type mice

gliosis ( J:61490 )

• gliosis spreads throughout the lateral and medial striatum over time

astrocytosis ( J:61490 )

• mice exhibit reactive astrocytosis in the striatum that spreads over time

• however, treatment with doxycycline after the onset of symptoms reduces astrocytosis

neuronal intranuclear inclusions ( J:61490 )

• mice develop neuronal intranuclear and extranuclear inclusion

• however, treatment with doxycycline after the onset of symptoms alleviates inclusions

behavior/neurological

decreased grooming behavior ( J:61490 )

• in older mice with tremors

limb grasping ( J:61490 )

• beginning at 4 weeks, some mice exhibit limb grasping when suspended

• by 8 weeks, all mice display clasping that can last after mice are released

• however, treatment with doxycycline after the onset of symptoms reduces glasping behavior and duration

dystonia ( J:61490 )

• mice exhibit progressive motor dysfunction with choreic and dystonic movements, and parkinsonism

tremors ( J:61490 )

• mild tremors begin at 20 weeks in some mice

• in some mice tremors develop into a jerking motion

decreased locomotor activity ( J:61490 )

• at 36 weeks

muscle

dystonia ( J:61490 )

• mice exhibit progressive motor dysfunction with choreic and dystonic movements, and parkinsonism

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Huntington's disease		DOID:12858	OMIM:143100	J:61490

Genotype
MGI:5694057

cx53

• Allelic Composition: Tg(Camk2a-tTA)1Mmay/0; Tg(tetO-DRD3)3-10Kndl/0
• Genetic Background: involves: C57BL/6 * CBA

behavior/neurological

abnormal emotion/affect behavior ( J:225565 )

• reduced number of total lever presses in progressive ratio (PR) measure of incentive motivation

• mice exhibit less motivation to obtain food reward

Genotype
MGI:3838963

cx54

• Allelic Composition: Tg(Camk2a-tTA)1Mmay/0; Tg(tetO-DISC1*)1001Plet/0
• Genetic Background: involves: C57BL/6 * CBA * SJL

behavior/neurological

abnormal spatial reference memory ( 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

increased locomotor activity ( J:146881 )

♂ • male mutants show higher degree of spontaneous locomotor activity than wild-type littermate controls during a 20-hour period

abnormal social/conspecific interaction behavior ( J:146881 )

♂ • male mutants spend significantly less time in non-aggressive social interaction with other males

increased aggression towards mice ( J:146881 )

♂ • males display increased aggressiveness toward other males, with an increase in number of attacks

nervous system

abnormal lateral ventricle morphology ( J:146881 )

• volume is significantly increased, with no change in total brain volume

abnormal neuron morphology ( J:146881 )

• cultured control neurons grow more complex neurite arbors than mutant neurons (for 20-100 um rings centered on neuron soma)

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
schizophrenia 9		DOID:0070085	OMIM:604906	J:146881

Genotype
MGI:6287125

cx55

• Allelic Composition: Tg(tetO-DISC1*)70Plet/0; Tg(Camk2a-tTA)1Mmay/0
• Genetic Background: involves: C57BL/6 * CBA * SJL

behavior/neurological

abnormal spatial reference memory ( 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 located

increased locomotor activity ( J:146881 )

♂ • males exhibit greater spontaneous locomotor activity during the dark period of testing

abnormal social/conspecific interaction behavior ( J:146881 )

♂ • males display increased aggressiveness toward other males, with an increase in number of attacks

increased aggression towards male mice ( J:146881 )

♂ • males spend less time in social non-aggressive interaction with other males

nervous system

enlarged lateral ventricles ( J:146881 )

• volume of the lateral ventricles is increased in 9 month old mice

• however, total brain volume is normal

abnormal neuron morphology ( J:146881 )

• primary cortical neuron cultures exhibit reduced neurite complexity

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
schizophrenia 9		DOID:0070085	OMIM:604906	J:146881

Genotype
MGI:5316005

cx56

• Allelic Composition: Tg(Camk2a-tTA)1Mmay/0; Tg(tetO-COX8A/PstI*)1Ctm/0
• Genetic Background: involves: C57BL/6 * CBA * SJL

mortality/aging

premature death ( 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

behavior/neurological

limb grasping ( J:145737 )

• mutants grown in the absence of Dox develop an abnormal limb-clasping behavior at 2 months of age

• mutants grown in the presence of Dox from E0 to P21, however, do not exhibit this limb-clasping behavior

decreased locomotor activity ( 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

Genotype
MGI:5634716

cx57

• Allelic Composition: Tg(Camk2a-tTA)1Mmay/0; Tg(tetO-Mtor*)#Atai/0
• Genetic Background: involves: C57BL/6 * DBA/2 * ICR

behavior/neurological

decreased locomotor activity ( J:211789 )

• withdrawal of doxycycline after administrating it for the first three weeks of life results in hypoactivity from 6 weeks of age

seizures ( J:211789 )

• in the absence of doxycycline, mice show spontaneous behavioral seizures around 2 weeks of age accompanied by abnormal local field potentials

• 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

• administration of doxycycline or rapamycin suppresses epileptic seizures

growth/size/body

megacephaly ( J:211789 )

• in the absence of doxycycline, mice show macrocephaly with abnormal cortical cytoarchitecture

• withdrawal of doxycycline after administrating it for the first three weeks of life results is macrocephaly without affecting the arrangement of the cortical layer

postnatal growth retardation ( J:211789 )

• in the absence of doxycycline, mice exhibit severe growth retardation from P10

hematopoietic system

microgliosis ( 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

• 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

immune system

microgliosis ( 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

• 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

mortality/aging

premature death ( 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

• administration of doxycycline or rapamycin suppresses lethality

postnatal lethality ( J:211789 )

• in the absence of doxycycline, mice die at 15-20 days of age

nervous system

seizures ( J:211789 )

• in the absence of doxycycline, mice show spontaneous behavioral seizures around 2 weeks of age accompanied by abnormal local field potentials

• 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

• administration of doxycycline or rapamycin suppresses epileptic seizures

microgliosis ( 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

• 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

abnormal cerebral cortex morphology ( J:211789 )

• cortical hypertrophy is seen at P12 in the absence of doxycycline

• in the absence of doxycycline, cortical lamination is disrupted

• 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

• administration of doxycycline or rapamycin suppresses cortical hypertrophy

thickened cerebral cortex ( J:211789 )

• in the absence of doxycycline, cortical thickness is increased

• withdrawal of doxycycline after administrating it for the first three weeks of life results in thickened cerebral cortex at 6-7 weeks of age

abnormal neuron morphology ( J:211789 )

• in the absence of doxycycline, soma size of cortical neurons is increased

• 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

neuronal cytoplasmic inclusions ( J:211789 )

• in the absence of doxycycline, mice exhibit an accumulation of ubiquitin-positive inclusions in neurons of the cortex at P2

• 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

neurodegeneration ( J:211789 )

• mice exhibit neurodegeneration after doxycycline removal

Genotype
MGI:3653709

cx58

• Allelic Composition: Tg(Camk2a-tTA)1Mmay/0; Tg(tetO-CDK5R1/GFP)337Lht/0
• Genetic Background: involves: C57BL/6J

growth/size/body

decreased body weight ( 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

nervous system

amyloid beta deposits ( 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

decreased brain weight ( J:104240 , 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)

abnormal forebrain morphology ( 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

abnormal hippocampus morphology ( 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

hippocampal neuron degeneration ( J:177847 )

• 50% reduction in the number of NeuN-positive cells in hippocampal area CA1 in 6-week induced mice

thin cerebral cortex ( 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

forebrain atrophy ( J:104240 )

• induced transgenic mice at 12 weeks postnatal display significant forebrain atrophy with decrease in forebrain mass

neurofibrillary tangles ( 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

• other methosds also identify neurofibrillary tangle-like structures in the cerebral cortex, hippocampus and entorhinal cortex of transgenic mice

• 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

gliosis ( J:104240 )

• reactive astrogliosis is increased throughout the cortex and hippocampus of mutants evident by an increase in radial and stellate-shaped astrocytes

astrocytosis ( J:177847 )

• reactive astrogliosis is seen in the cortex and hippocampus in 6-week induced mice

abnormal synapse morphology ( 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

impaired synaptic plasticity ( J:177847 )

• mice exhibit impaired synaptic plasticity following a 6-week induction

reduced long-term potentiation ( J:177847 )

• mice exhibit diminished CA1 long term potentiation (LTP) following a 6-week induction

behavior/neurological

impaired contextual conditioning behavior ( 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

homeostasis/metabolism

amyloid beta deposits ( 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

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Alzheimer's disease		DOID:10652		J:177847

Genotype
MGI:5555967

cx59

• Allelic Composition: Tg(Camk2a-tTA)1Mmay/0; Tg(tetO-Rai1,-EGFP)479Walz/0
• Genetic Background: involves: C57BL/6J * CBA/J

growth/size/body

decreased body weight ( J:207141 )

• mutants start to show lower weight at 2 months of age

• mutants treated with Dox to turn off transgene expression from conception to 3 months of age show normal weight

• 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

• 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

behavior/neurological

impaired contextual conditioning behavior ( J:207141 )

• mutants show less freezing in the contextual fear test, indicating that learning and/or memory are impaired

• mutants treated with Dox to turn off transgene expression from conception to 3 months of age show normal contextual memory

• 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

impaired cued conditioning behavior ( J:207141 )

• mutants show less freezing in the sound cued fear tests, indicating that learning and/or memory are impaired

• 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

• 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

increased locomotor activity ( J:207141 )

• in the open field, mutants show an increase in total distance traveled indicating hyperactivity

• however anxiety-like behavior is not observed and mice show normal sociability and preference for social novelty

• mutants treated with Dox to turn off transgene expression from conception to 3 months of age show normal activity

• 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

decreased vocalization ( J:207141 )

• lower percentage of vocalization, with mutants showing 8% vocalization compared to 29% in wild-type mice

adipose tissue

decreased abdominal fat pad weight ( J:207141 )

• mutants show lower abdominal fat weight

• mutants treated with Dox to turn off transgene expression from conception to 3 months of age show normal abdominal fat weight

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Potocki-Lupski syndrome		DOID:0060853	OMIM:610883	J:207141

Genotype
MGI:5555966

cx60

• Allelic Composition: Tg(Camk2a-tTA)1Mmay/0; Tg(tetO-Rai1,-EGFP)463Walz/0
• Genetic Background: involves: C57BL/6J * CBA/J

growth/size/body

decreased body weight ( J:207141 )

• mutants start to show lower weight at 4 months of age

behavior/neurological

impaired contextual conditioning behavior ( J:207141 )

• mutants show less freezing in the contextual fear test, indicating that learning and/or memory are impaired

impaired cued conditioning behavior ( J:207141 )

• mutants show less freezing in the sound cued fear tests, indicating that learning and/or memory are impaired

increased locomotor activity ( J:207141 )

• in the open field, mutants show an increase in total distance traveled indicating hyperactivity

• however, anxiety-like behavior is not observed and mice show normal sociability and preference for social novelty

decreased vocalization ( J:207141 )

• lower percentage of vocalization, with mutants showing 17% vocalization compared to 29% in wild-type mice

adipose tissue

decreased abdominal fat pad weight ( J:207141 )

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Potocki-Lupski syndrome		DOID:0060853	OMIM:610883	J:207141

Genotype
MGI:5491208

cx61

• Allelic Composition: Tg(Camk2a-tTA)1Mmay/0; Tg(tetO-LMNB1)AF1Yfu/0
• Genetic Background: involves: FVB

behavior/neurological

behavior/neurological phenotype ( J:197168 )

N • normal motor behavior

Genotype
MGI:5511058

cx62

• Allelic Composition: Tg(Camk2a-tTA)1Mmay/0; Fgf14^{Tg(tetO-MAPT*P301L)4510Kha}/Fgf14⁺
• Genetic Background: involves: FVB/N

behavior/neurological

decreased exploration in new environment ( J:102973 )

• reduction in exploration in open-field tests

abnormal spatial reference memory ( 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

• 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

• mutants exhibit cognitive impairments in the acquisition phases of the Morris water maze, showing a longer mean distance to locate the hidden platform

limb grasping ( J:102973 )

• clasping and limb retraction when lifted by the tail

dystonia ( J:102973 )

• develop dystonic posture with tail rigor at 9.5 months of age

impaired coordination ( J:102973 )

• mutants exhibit longer latencies to traverse a beam

impaired swimming ( 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

hunched posture ( J:102973 )

• from about 9.5 months of age, the most severely affected mutants develop hunched posture with hindlimb dysfunction and tail rigor

abnormal gait ( J:102973 )

• from about 9.5 months of age, the most severely affected mutants exhibit decreased ambulation

growth/size/body

weight loss ( J:102973 )

• from about 9.5 months of age, the most severely affected mutants exhibit decreased body weight

nervous system

decreased brain weight ( J:102973 )

• 4-7% reduction in brain weight at 4 months of age

forebrain atrophy ( J:102973 )

• atrophy of the forebrain is seen by 5 months of age

neurofibrillary tangles ( J:102973 )

• age-dependent progression of tau processing that results in pathophysiological deposition of tau as mature tangles in the brain

• 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

• 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

tau protein deposits ( J:102973 )

• abnormal conformations of tau are present in the hippocampus and neocortex of 2.5-month old mutants

astrocytosis ( J:102973 )

• reactive astrocytes in forebrains of 10 month old mutants

abnormal corticospinal tract morphology ( J:102973 )

• atrophy of the dorsal corticospinal tracts accompanied by loss of neurofilament

neuron degeneration ( J:102973 )

• degeneration in the hippocampus and neocortex is seen in 10 month old mutants

hippocampal neuron degeneration ( J:102973 )

• massive neuronal loss, most apparent in the CA1 region of the hippocampus

abnormal spinal cord morphology ( J:102973 )

• spinal cords appear thinner, however, no decrease in motor neuron density is seen

muscle

dystonia ( J:102973 )

• develop dystonic posture with tail rigor at 9.5 months of age

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Alzheimer's disease		DOID:10652		J:102973
frontotemporal dementia		DOID:9255	OMIM:600274	J:102973

Genotype
MGI:4414670

cx63

• Allelic Composition: Tg(Camk2a-tTA)1Mmay/0; Tg(tetO-LRRK2)1Cai/0
• Genetic Background: Not Specified

nervous system

nervous system phenotype ( J:154755 )

N • neuronal processes are normal

Genotype
MGI:4414669

cx64

• Allelic Composition: Tg(Camk2a-tTA)1Mmay/0; Tg(tetO-LRRK2*G2019S)1Cai/0
• Genetic Background: Not Specified

nervous system

abnormal neurite morphology ( J:154755 )

• total neurite length is shortened compared to in wild-type mice

• neurons produce fewer neurites than in wild-type mice

• however, doxycyclin or forskolin treatment rescues the inhibited neurite growth

abnormal axon morphology ( J:154755 )

• the longest process corresponding to the axon is reduced in length compared to in wild-type mice

Genotype
MGI:5803805

tg65

• Allelic Composition: Tg(Camk2a-tTA)1Mmay/0
• Genetic Background: 129S6.Cg-Tg(Camk2a-tTA)1Mmay

nervous system

abnormal forebrain morphology ( J:235351 )

• reduced forebrain weight in 2-6, 13-17, and 24-27 month old mice

decreased dentate gyrus size ( J:235351 )

thin cerebellar granule layer ( J:235351 )

Genotype
MGI:5438789

tg66

• Allelic Composition: Tg(Camk2a-tTA)1Mmay/0
• Genetic Background: (B6.Cg-Tg(Camk2a-tTA)1Mmay x 129X1/SvJ)F1

behavior/neurological

impaired contextual conditioning behavior ( 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

nervous system

abnormal dentate gyrus morphology ( J:185792 )

• Background Sensitivity: width of granule cell layer is 27% thinner than controls and the C57BL/6 congenic background

hippocampal neuron degeneration ( J:185792 )

• Background Sensitivity: width of granule cell layer is 27% thinner than controls and the C57BL/6 congenic background

Genotype
MGI:5438785

tg67

• Allelic Composition: Tg(Camk2a-tTA)1Mmay/0
• Genetic Background: (B6.Cg-Tg(Camk2a-tTA)1Mmay x C3H/HeJ)F1

nervous system

abnormal dentate gyrus morphology ( J:185792 )

• Background Sensitivity: width of granule cell layer is 14% thinner than controls and the C57BL/6 congenic background

hippocampal neuron degeneration ( J:185792 )

• Background Sensitivity: width of granule cell layer is 14% thinner than controls and the C57BL/6 congenic background

Genotype
MGI:5438807

tg68

• Allelic Composition: Tg(Camk2a-tTA)1Mmay/0
• Genetic Background: (B6.Cg-Tg(Camk2a-tTA)1Mmay x C3H/HeJ)F1 x C3H/HeJ

nervous system

abnormal dentate gyrus morphology ( J:185792 )

• Background Sensitivity: width of granule cell layer is 29% thinner than controls and C57BL/6 congenic background

hippocampal neuron degeneration ( J:185792 )

• Background Sensitivity: width of granule cell layer is 29% thinner than controls and C57BL/6 congenic background

Genotype
MGI:5438788

tg69

• Allelic Composition: Tg(Camk2a-tTA)1Mmay/0
• Genetic Background: (B6.Cg-Tg(Camk2a-tTA)1Mmay x CBA/J)F1

nervous system

abnormal dentate gyrus morphology ( J:185792 )

• Background Sensitivity: width of granule cell layer is 30% thinner than controls and the C57BL/6 congenic background

hippocampal neuron degeneration ( J:185792 )

• Background Sensitivity: width of granule cell layer is 30% thinner than controls and the C57BL/6 congenic background

Genotype
MGI:5438790

tg70

• Allelic Composition: Tg(Camk2a-tTA)1Mmay/0
• Genetic Background: (B6.Cg-Tg(Camk2a-tTA)1Mmay x DBA/1J)F1

nervous system

abnormal dentate gyrus morphology ( J:185792 )

• Background Sensitivity: width of granule cell layer is 17% thinner than controls and the C57BL/6 congenic background

hippocampal neuron degeneration ( J:185792 )

• Background Sensitivity: width of granule cell layer is 17% thinner than controls and the C57BL/6 congenic background

Genotype
MGI:5438792

tg71

• Allelic Composition: Tg(Camk2a-tTA)1Mmay/0
• Genetic Background: (B6.Cg-Tg(Camk2a-tTA)1Mmay x FVB/NJ)F1

nervous system

abnormal dentate gyrus morphology ( J:185792 )

• Background Sensitivity: width of dentate gyrus granule cell layer is 21% thinner than controls and the C57BL/6 congenic background

• however, doxycycline administered in the first 6 weeks of life protects against cell loss

hippocampal neuron degeneration ( J:185792 )

• Background Sensitivity: width of dentate gyrus granule cell layer is 21% thinner than controls and the C57BL/6 congenic background

• however, doxycycline administered in the first 6 weeks of life protects against cell loss

Genotype
MGI:5438801

tg72

• Allelic Composition: Tg(Camk2a-tTA)1Mmay/0
• Genetic Background: involves: C3H/HeJ * C57BL/6 * CBA

nervous system

abnormal dentate gyrus morphology ( J:185792 )

• Background Sensitivity: granule cell layer of the dentate gyrus is reduced and disorganized in 2 month old mice as compared to non-transgenic controls and the C57BL/6 congenic background

• Background Sensitivity: cell loss is not observed in 2 week old mice

• Background Sensitivity: width of granule cell layer is 42% thinner than controls by 2-4 months

• Background Sensitivity: width of granule cell layer is 68% thinner than controls by 6-9 months

• however, when mice are reared on doxycycline, cell loss is not observed

hippocampal neuron degeneration ( J:185792 )

• neuronal degeneration is progressive

Genotype
MGI:5438794

tg73

• Allelic Composition: Tg(Camk2a-tTA)1Mmay/?
• Genetic Background: B6.Cg-Tg(Camk2a-tTA)1Mmay

behavior/neurological

abnormal long-term spatial reference memory ( J:185792 )

• mice swim less distance in the target quadrant than controls when tested for long-term recall suggesting a memory consolidation impairment

nervous system

nervous system phenotype ( J:185792 )

N • Background Sensitivity: no evidence of overt dentate degeneration on the C57BL/6 congenic background as compared to C3H/He and CBA genetic backgrounds

N • granule cell layer is similar to control at all time points studied