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Phenotypes associated with this allele
Allele Symbol
Allele Name
Allele ID
Gt(ROSA)26Sortm1(DTA)Jpmb
targeted mutation 1, Juan Pedro Martinez-Barbera
MGI:3610389
Summary 18 genotypes
Jump to Allelic Composition Genetic Background Genotype ID
hm1
Gt(ROSA)26Sortm1(DTA)Jpmb/Gt(ROSA)26Sortm1(DTA)Jpmb either: (involves: 129S/SvEv * C57BL/6) or (involves: 129S/SvEv * CD-1) MGI:3611574
cn2
Gt(ROSA)26Sortm1(DTA)Jpmb/Gt(ROSA)26Sor+
Nkx2-5tm1(cre)Rjs/Nkx2-5+
either: (involves: 129S/SvEv * 129S7/SvEvBrd * C57BL/6) or (involves: 129S/SvEv * 129S7/SvEvBrd * CD-1) MGI:3611572
cn3
Gt(ROSA)26Sortm1(DTA)Jpmb/Gt(ROSA)26Sor+
H2az2Tg(Wnt1-cre)11Rth/0
either: (involves: 129S/SvEv * C57BL/6 * CBA) or (involves: 129S/SvEv * C57BL/6 * CBA * CD-1) MGI:3611573
cn4
Gt(ROSA)26Sortm1(DTA)Jpmb/Gt(ROSA)26Sor+
Calcatm1.1(cre/ERT2)Ptch/Calca+
involves: 129P2/OlaHsd * 129S/SvEv MGI:5460837
cn5
Gt(ROSA)26Sortm1(DTA)Jpmb/Gt(ROSA)26Sor+
Tg(Trpv1-cre)1Hoon/0
involves: 129S1/Sv MGI:5013957
cn6
Gdnftm1(cre/ERT2)Cos/Gdnf+
Gt(ROSA)26Sortm1(DTA)Jpmb/Gt(ROSA)26Sor+
Spry1tm1.1Jdli/Spry1+
involves: 129S1/Sv * 129S6/SvEvTac * 129X1/SvJ * C57BL/6J MGI:5553081
cn7
Gdnftm1(cre/ERT2)Cos/Gdnf+
Gt(ROSA)26Sortm1(DTA)Jpmb/Gt(ROSA)26Sor+
involves: 129S6/SvEvTac * C57BL/6J MGI:5553068
cn8
Gt(ROSA)26Sortm1(DTA)Jpmb/Gt(ROSA)26Sor+
Tg(Smad7-cre)1Sjc/0
involves: 129S/Sv * C3HeB/FeJ MGI:4352743
cn9
Gt(ROSA)26Sortm1(DTA)Jpmb/Gt(ROSA)26Sor+
Hcn4tm1(cre/ERT2)Anlu/Hcn4+
involves: 129S/SvEv MGI:5432113
cn10
Dph1tm2Bhr/Dph1tm2Bhr
Gt(ROSA)26Sortm1(DTA)Jpmb/Gt(ROSA)26Sor+
Mesp1tm2(cre)Ysa/Mesp1+
involves: 129S/SvEv * 129S4/SvJae * C57BL/6J * C57BL/6NCrlj * CBA/JNCrlj MGI:5659981
cn11
Dph1tm2Bhr/Dph1+
Gt(ROSA)26Sortm1(DTA)Jpmb/Gt(ROSA)26Sor+
Mesp1tm2(cre)Ysa/Mesp1+
involves: 129S/SvEv * 129S4/SvJae * C57BL/6J * C57BL/6NCrlj * CBA/JNCrlj MGI:5659980
cn12
Dph1tm2Bhr/Dph1+
Gt(ROSA)26Sortm1(DTA)Jpmb/Gt(ROSA)26Sor+
H2az2Tg(Wnt1-cre)11Rth/0
involves: 129S/SvEv * 129S4/SvJae * C57BL/6J * CBA/J MGI:5659976
cn13
Dph1tm2Bhr/Dph1tm2Bhr
Gt(ROSA)26Sortm1(DTA)Jpmb/Gt(ROSA)26Sor+
H2az2Tg(Wnt1-cre)11Rth/0
involves: 129S/SvEv * 129S4/SvJae * C57BL/6J * CBA/J MGI:5659977
cn14
Gt(ROSA)26Sortm1(DTA)Jpmb/Gt(ROSA)26Sor+
Kittm1(cre/ERT2)Dsa/Kit+
involves: 129S/SvEv * 129S6/SvEvTac * C57BL/6 MGI:5545742
cn15
Gt(ROSA)26Sortm1(DTA)Jpmb/Gt(ROSA)26Sor+
Tg(Slc16a8-cre/ERT2,-EGFP)1Moss/0
involves: 129S/SvEv * C57BL/6 * CBA MGI:4399750
cn16
Gt(ROSA)26Sortm1(DTA)Jpmb/Gt(ROSA)26Sor+
Tg(Plp1-cre/ERT)3Pop/0
involves: 129S/SvEv * C57BL/6 * DBA/2 MGI:5796111
cn17
Gt(ROSA)26Sortm1(DTA)Jpmb/Gt(ROSA)26Sor+
Mesp1tm2(cre)Ysa/Mesp1+
involves: 129S/SvEv * C57BL/6NCrlj * CBA/JNCrlj MGI:5659978
cn18
Gt(ROSA)26Sortm1(DTA)Jpmb/Gt(ROSA)26Sortm1(DTA)Jpmb
Tg(KRT14-cre/ERT)20Efu/?
involves: 129S/SvEv * CD-1 MGI:5289774


Genotype
MGI:3611574
hm1
Allelic
Composition
Gt(ROSA)26Sortm1(DTA)Jpmb/Gt(ROSA)26Sortm1(DTA)Jpmb
Genetic
Background
either: (involves: 129S/SvEv * C57BL/6) or (involves: 129S/SvEv * CD-1)
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Gt(ROSA)26Sortm1(DTA)Jpmb mutation (2 available); any Gt(ROSA)26Sor mutation (784 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
normal phenotype
• homozygotes are viable and fertile with no gross abnormalities




Genotype
MGI:3611572
cn2
Allelic
Composition
Gt(ROSA)26Sortm1(DTA)Jpmb/Gt(ROSA)26Sor+
Nkx2-5tm1(cre)Rjs/Nkx2-5+
Genetic
Background
either: (involves: 129S/SvEv * 129S7/SvEvBrd * C57BL/6) or (involves: 129S/SvEv * 129S7/SvEvBrd * CD-1)
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Gt(ROSA)26Sortm1(DTA)Jpmb mutation (2 available); any Gt(ROSA)26Sor mutation (784 available)
Nkx2-5tm1(cre)Rjs mutation (1 available); any Nkx2-5 mutation (17 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
mortality/aging

cardiovascular system
• at the 12-14 somite stage no heart is present

embryo
• at E9.5 embryos are very small and some are partially resorbed

growth/size/body
• at E9.5 embryos are very small and some are partially resorbed




Genotype
MGI:3611573
cn3
Allelic
Composition
Gt(ROSA)26Sortm1(DTA)Jpmb/Gt(ROSA)26Sor+
H2az2Tg(Wnt1-cre)11Rth/0
Genetic
Background
either: (involves: 129S/SvEv * C57BL/6 * CBA) or (involves: 129S/SvEv * C57BL/6 * CBA * CD-1)
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Gt(ROSA)26Sortm1(DTA)Jpmb mutation (2 available); any Gt(ROSA)26Sor mutation (784 available)
H2az2Tg(Wnt1-cre)11Rth mutation (2 available); any H2az2 mutation (25 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
nervous system
• at E9.5 and E10.5, the cranial neural tube is open dorsally
• at E9.5 and E10.5, the isthmus (the constriction of the neural tube at the midbrain hindbrain boundary) is absent
• at E9.5 and E10.5 the brain rostral to the otic vesicle is significantly smaller

embryo
• at E9.5 and E10.5, the cranial neural tube is open dorsally




Genotype
MGI:5460837
cn4
Allelic
Composition
Gt(ROSA)26Sortm1(DTA)Jpmb/Gt(ROSA)26Sor+
Calcatm1.1(cre/ERT2)Ptch/Calca+
Genetic
Background
involves: 129P2/OlaHsd * 129S/SvEv
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Calcatm1.1(cre/ERT2)Ptch mutation (0 available); any Calca mutation (16 available)
Gt(ROSA)26Sortm1(DTA)Jpmb mutation (2 available); any Gt(ROSA)26Sor mutation (784 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
respiratory system
• clara cell numbers recover after tamoxifen and/or naphthalene lung injury regardless of presence or absence of pulmonary neuroendocrine cells
• pulmonary neuroendocrine cells ablated by tamoxifen treatment are not replaced at 1, 6, 10, and 12 months after treatment
• naphthalene lung injury fails to induce restoration of this cell type




Genotype
MGI:5013957
cn5
Allelic
Composition
Gt(ROSA)26Sortm1(DTA)Jpmb/Gt(ROSA)26Sor+
Tg(Trpv1-cre)1Hoon/0
Genetic
Background
involves: 129S1/Sv
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Gt(ROSA)26Sortm1(DTA)Jpmb mutation (2 available); any Gt(ROSA)26Sor mutation (784 available)
Tg(Trpv1-cre)1Hoon mutation (0 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
behavior/neurological
N
• animals do not exhibit any signs of self-mutilation or taste response deficits
• animals have normal mechanosensory responses following nerve ligation or sensitization by inflammation; responses in assays for touch and pinch assays are identical to controls
• rotarod results are normal, indicating no loss of proprioceptive function
• responses to capsaicin and mustard oil in eye wipe and paw injection paradigms are eliminated
• animals display no 'wet-dog shakes' in response to icilin injection which gives perception of cooling, whereas controls show robust characteristic responses
• mice are insensitive to noxious heat compared to controls (animals do not display protective thermosensory responses in hot plate paw withdrawal or tail-flick assays)
• mice show no reaction to a cold plate assay or preference in a 2-temperature choice test (30 C vs 5 C)

nervous system
N
• distribution and arrangement of dorsal horn interneurons is not significantly different from wild-type animals
• recordings from sciatic nerve in response to stimulation of the foot (by brush, von Frey microfilaments, or vibration) are not different than in controls
• rotarod results are normal, indicating no loss of proprioceptive function
• mutants have reduced numbers of TRPV2-containing sensory neurons

homeostasis/metabolism
• in response to IP injection of capsaicin, mice do not exhibit the profound hypothermia that is shown by treated controls
• mutants are unable to maintain their body temperature than wild-type controls when the environmental temperature is changed
• animals exhibit a greater hypothermic response than wild-type upon antigen injection, with slower re-establishment of normal resting temperature
• animals show a greater temperature change in response to mild fever induced by Il-1beta injection relative to wild-type

immune system
• responses to ATP, prostaglandins, bradykinin, histamine and serotonin are lost in mutants; significant loss of neurogenic inflammation is observed, and significantly less inflammation occurs in response to carageenan challenge

integument
• mutants display complete loss of behavioral responses to injection of pruritogenic compounds




Genotype
MGI:5553081
cn6
Allelic
Composition
Gdnftm1(cre/ERT2)Cos/Gdnf+
Gt(ROSA)26Sortm1(DTA)Jpmb/Gt(ROSA)26Sor+
Spry1tm1.1Jdli/Spry1+
Genetic
Background
involves: 129S1/Sv * 129S6/SvEvTac * 129X1/SvJ * C57BL/6J
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Gdnftm1(cre/ERT2)Cos mutation (1 available); any Gdnf mutation (12 available)
Gt(ROSA)26Sortm1(DTA)Jpmb mutation (2 available); any Gt(ROSA)26Sor mutation (784 available)
Spry1tm1.1Jdli mutation (0 available); any Spry1 mutation (11 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
renal/urinary system
• with tamoxifen treatment at E12.5, presence of a single copy of Spry1 only marginally improves the hypoplasia observed at E19.5




Genotype
MGI:5553068
cn7
Allelic
Composition
Gdnftm1(cre/ERT2)Cos/Gdnf+
Gt(ROSA)26Sortm1(DTA)Jpmb/Gt(ROSA)26Sor+
Genetic
Background
involves: 129S6/SvEvTac * C57BL/6J
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Gdnftm1(cre/ERT2)Cos mutation (1 available); any Gdnf mutation (12 available)
Gt(ROSA)26Sortm1(DTA)Jpmb mutation (2 available); any Gt(ROSA)26Sor mutation (784 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
renal/urinary system
• when tamoxifen is administered at E12.5, mutant kidneys have about half the number of glomeruli (48%) at E19.5
• glomerulus number does not recover as well as kidney size with numbers only 57.6% of normal at P50
• when tamoxifen is administered at E12.5, fetuses develop severe renal hypoplasia by E14.5, with kidney growth rate reduced relative to wild-type
• nephrogenic zone appears normal at E19.5
• when tamoxifen is administered at E12.5, at E19.5 kidneys are 55.7% of normal size (based on maximal cross-sectional area); normal gross organization into cortex, medulla and papilla remains
• recovery from tamoxifen treatment at E12.5 is observed postnatally with kidney size reaching 70.4% of control size at P14 and 89.3% at P50
• with tamoxifen treatment at E14.5, resulting kidney morphology is similar at birth with reduced hypoplasia; kidneys are 89% of control size
• when tamoxifen is administered at E9.5, about half the fetuses have severe renal hypoplasia with kidneys about 46.6% of the size of controls
• when tamoxifen is administered at E9.5, about half the fetuses display renal agenesis at E18.5




Genotype
MGI:4352743
cn8
Allelic
Composition
Gt(ROSA)26Sortm1(DTA)Jpmb/Gt(ROSA)26Sor+
Tg(Smad7-cre)1Sjc/0
Genetic
Background
involves: 129S/Sv * C3HeB/FeJ
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Gt(ROSA)26Sortm1(DTA)Jpmb mutation (2 available); any Gt(ROSA)26Sor mutation (784 available)
Tg(Smad7-cre)1Sjc mutation (0 available)
phenotype observed in females
phenotype observed in males
N normal phenotype

Cardiovascular abnormalities in Gt(ROSA)26Sortm1(DTA)Jpmb/Gt(ROSA)26Sor+ Tg(Smad7-cre)1Sjc/0 embryos

mortality/aging
• cardiovascular developmental abnormalities result in in utero death

embryo
• yolk sacs of mutant embryos have almost no vasculature compared to controls
• observed in E10.5 embryos

cardiovascular system
N
• in mutants, ventricular myocardium and endothelial layer are intact
• vessels are weakened and hemorrhagic in embryos
• dorsal aorta is fragmented and contains only a few smooth muscle cells
• yolk sacs of mutant embryos have almost no vasculature compared to controls
• atrioventricular (AV) cushion region is largely absent in mutants
• cushion hypoplasia is observed at E10
• E10.5 embryos have smaller hearts relative to controls
• E10.5 embryos are hemorrhagic

craniofacial
• observed in E10.5 embryos




Genotype
MGI:5432113
cn9
Allelic
Composition
Gt(ROSA)26Sortm1(DTA)Jpmb/Gt(ROSA)26Sor+
Hcn4tm1(cre/ERT2)Anlu/Hcn4+
Genetic
Background
involves: 129S/SvEv
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Gt(ROSA)26Sortm1(DTA)Jpmb mutation (2 available); any Gt(ROSA)26Sor mutation (784 available)
Hcn4tm1(cre/ERT2)Anlu mutation (0 available); any Hcn4 mutation (38 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
muscle
• ablation of sinoatrial node cells following tamoxifen treatment that varies depending on tamoxifen dose

mortality/aging
• approximately 20% of mice die suddenly with no ante-mortem indication of illness within 60 days after high dose tamoxifen treatment

cardiovascular system
• ablation of sinoatrial node cells following tamoxifen treatment that varies depending on tamoxifen dose
• tamoxifen induced ablation of sinoatrial node cells is accompanied by a destructive fibrosis of nodal tissue
• following 5 days of tamoxifen treatment show alternating periods of slow and fast frequencies in R-R tachograms
• alterations of long electrical standstills (sinus pauses) and intermittent rapid atrial activity following tamoxifen treatment
• following 5 days of tamoxifen treatment absolute value of the maximally (isoprenaline) stimulated heart rate remained low
• following 5 days of high or low dose tamoxifen treatment heart rate falls by about 40 - 50% or 12%, respectively
• variety of cardiac rhythm disturbances; including sino-atrial arrhythmia, sino-atrial pause and to a minor extent supraventricular or ventricular tachycardia, following tamoxifen treatment
• complete heart block some weeks after tamoxifen treatment
• following tamoxifen treatment
• progressive prolongation of the P-R interval tends to result in complete isolated contraction of atria and ventricles with high dose tamoxifen treatment

Mouse Models of Human Disease
DO ID OMIM ID(s) Ref(s)
sick sinus syndrome DOID:13884 OMIM:163800
OMIM:608567
J:186021




Genotype
MGI:5659981
cn10
Allelic
Composition
Dph1tm2Bhr/Dph1tm2Bhr
Gt(ROSA)26Sortm1(DTA)Jpmb/Gt(ROSA)26Sor+
Mesp1tm2(cre)Ysa/Mesp1+
Genetic
Background
involves: 129S/SvEv * 129S4/SvJae * C57BL/6J * C57BL/6NCrlj * CBA/JNCrlj
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Dph1tm2Bhr mutation (0 available); any Dph1 mutation (20 available)
Gt(ROSA)26Sortm1(DTA)Jpmb mutation (2 available); any Gt(ROSA)26Sor mutation (784 available)
Mesp1tm2(cre)Ysa mutation (1 available); any Mesp1 mutation (14 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
mortality/aging
N
• embryos are obtained unlike in triple mutants that are heterozygous for the Dph1 allele




Genotype
MGI:5659980
cn11
Allelic
Composition
Dph1tm2Bhr/Dph1+
Gt(ROSA)26Sortm1(DTA)Jpmb/Gt(ROSA)26Sor+
Mesp1tm2(cre)Ysa/Mesp1+
Genetic
Background
involves: 129S/SvEv * 129S4/SvJae * C57BL/6J * C57BL/6NCrlj * CBA/JNCrlj
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Dph1tm2Bhr mutation (0 available); any Dph1 mutation (20 available)
Gt(ROSA)26Sortm1(DTA)Jpmb mutation (2 available); any Gt(ROSA)26Sor mutation (784 available)
Mesp1tm2(cre)Ysa mutation (1 available); any Mesp1 mutation (14 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
mortality/aging




Genotype
MGI:5659976
cn12
Allelic
Composition
Dph1tm2Bhr/Dph1+
Gt(ROSA)26Sortm1(DTA)Jpmb/Gt(ROSA)26Sor+
H2az2Tg(Wnt1-cre)11Rth/0
Genetic
Background
involves: 129S/SvEv * 129S4/SvJae * C57BL/6J * CBA/J
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Dph1tm2Bhr mutation (0 available); any Dph1 mutation (20 available)
Gt(ROSA)26Sortm1(DTA)Jpmb mutation (2 available); any Gt(ROSA)26Sor mutation (784 available)
H2az2Tg(Wnt1-cre)11Rth mutation (2 available); any H2az2 mutation (25 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
growth/size/body
• loss of head structures in E10.5 embryos




Genotype
MGI:5659977
cn13
Allelic
Composition
Dph1tm2Bhr/Dph1tm2Bhr
Gt(ROSA)26Sortm1(DTA)Jpmb/Gt(ROSA)26Sor+
H2az2Tg(Wnt1-cre)11Rth/0
Genetic
Background
involves: 129S/SvEv * 129S4/SvJae * C57BL/6J * CBA/J
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Dph1tm2Bhr mutation (0 available); any Dph1 mutation (20 available)
Gt(ROSA)26Sortm1(DTA)Jpmb mutation (2 available); any Gt(ROSA)26Sor mutation (784 available)
H2az2Tg(Wnt1-cre)11Rth mutation (2 available); any H2az2 mutation (25 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
growth/size/body
N
• embryos retain their heads and appear normal at E10.5




Genotype
MGI:5545742
cn14
Allelic
Composition
Gt(ROSA)26Sortm1(DTA)Jpmb/Gt(ROSA)26Sor+
Kittm1(cre/ERT2)Dsa/Kit+
Genetic
Background
involves: 129S/SvEv * 129S6/SvEvTac * C57BL/6
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Gt(ROSA)26Sortm1(DTA)Jpmb mutation (2 available); any Gt(ROSA)26Sor mutation (784 available)
Kittm1(cre/ERT2)Dsa mutation (0 available); any Kit mutation (148 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
muscle
• tamoxifen-treated mice show dysrhythmia resulting from uncoordinated spontaneous contractions and lack of slow-wave type electrical activity

digestive/alimentary system
• significantly disturbed after 3 days of tamoxifen treatment (which results in loss of more than 50% of insterstitial cells of Cajal (ICCs)
• tamoxifen-treated mice show dysrhythmia resulting from uncoordinated spontaneous contractions and lack of slow-wave type electrical activity
• total GI transit time is increased to more than 5 hours; similar transit time is measured in tamoxifen-treated mutants that have been repopulated with wild-type mast cells (by adaptive BM transplant)
• tamoxifen-treated mice have delayed gastric emptying

nervous system
• in tamoxifen treated mice, excitatory enteric neurotransmission is blocked as result of ICC depletion




Genotype
MGI:4399750
cn15
Allelic
Composition
Gt(ROSA)26Sortm1(DTA)Jpmb/Gt(ROSA)26Sor+
Tg(Slc16a8-cre/ERT2,-EGFP)1Moss/0
Genetic
Background
involves: 129S/SvEv * C57BL/6 * CBA
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Gt(ROSA)26Sortm1(DTA)Jpmb mutation (2 available); any Gt(ROSA)26Sor mutation (784 available)
Tg(Slc16a8-cre/ERT2,-EGFP)1Moss mutation (0 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
vision/eye
N
• despite loss of retinal pigment epithelia in tamoxifen treated mice, the retinal pigment epithelial barrier function is maintained and retinal vasculature is normal
• loss of retinal pigment epithelium in tamoxifen treated mice is compensated by increased size of neighboring cells without loss of cell thickness preventing gaps in the epithelium
• 6 days after tamoxifen treatment, retinal pigment cells become round and are exuded from the retina
• 2 weeks after tamoxifen treatment, retinal pigment cells are enlarged and irregularly shaped with clumps of extruding cells
• 14 days after tamoxifen treatment the retinal pigment cells are reduced 68% compared to in mice lacking the cre transgene
• however, loss of retinal pigment cells is stabilized between day 14 and 6 months
• following tamoxifen treatment, mice develop variable retinal folds termed rossetting unlike wild-type mice
• under scotopic conditions at 6 weeks and 6 months, tamoxifen-treated mice exhibit decreased a and b wave amplitudes compared with wild-type mice

pigmentation
• loss of retinal pigment epithelium in tamoxifen treated mice is compensated by increased size of neighboring cells without loss of cell thickness preventing gaps in the epithelium
• however, loss of retinal pigment cells is stabilized between day 14 and 6 months
• 6 days after tamoxifen treatment, retinal pigment cells become round and are exuded from the retina
• 2 weeks after tamoxifen treatment, retinal pigment cells are enlarged and irregularly shaped with clumps of extruding cells
• 14 days after tamoxifen treatment the retinal pigment cells are reduced 68% compared to in mice lacking the cre transgene




Genotype
MGI:5796111
cn16
Allelic
Composition
Gt(ROSA)26Sortm1(DTA)Jpmb/Gt(ROSA)26Sor+
Tg(Plp1-cre/ERT)3Pop/0
Genetic
Background
involves: 129S/SvEv * C57BL/6 * DBA/2
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Gt(ROSA)26Sortm1(DTA)Jpmb mutation (2 available); any Gt(ROSA)26Sor mutation (784 available)
Tg(Plp1-cre/ERT)3Pop mutation (2 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
mortality/aging
• about 50% of mice die 52 weeks after tamoxifen injection

nervous system
• mice exhibit seizures starting around 40 weeks after tamoxifen injection
• focal lesions in tamoxifen treated mice are sites of active inflammation, frequently infiltrated by T cells, and contain a high density of microglia or macrophages
• mice show increased CD3+ T cells in the CNS as early as 7 weeks after tamoxifen injection, increased numbers of CD4+ T cells in the CNS at 10 and 40 weeks after tamoxifen injection, and increased numbers of MHCII+B7+ (CD80+CD86+) dendritic cells at 40 weeks after tamoxifen injection
• all recovered tamoxifen-treated mice develop secondary, late-onset neurological symptoms and demyelinating disease starting around 40 weeks after injection
• mice injected with MOG(35-55)-coupled polylactic-co-glycolic acid nanoparticles 32 weeks after tamoxifen injection show inhibition of disease progression
• mice exhibit rare focal lesions in the brainstem, cerebellum, and spinal cord at 40 weeks after tamoxifen injection
• at 1 year after tamoxifen injection, focal lesions in these regions are no longer seen
• white matter lesions in tamoxifen injected mice show presence of macrophages containing myelin debris and unmyelinated axons, indicating ongoing demyelination
• tamoxifen treated mice exhibit loss of oligodendrocytes, peaking 5 weeks after injection and recovering by 10 weeks
• brainstem shows an approximate 50% decrease in oligodendrocytes at 1 year after tamoxifen treatment
• however, substantial oligodendrocyte loss in other CNS areas is not seen at 1 year after tamoxifen treatment
• thinner myelin in both tamoxifen treated and untreated mice (due to leakiness of the cre-expressing transgene)
• axonal loss in the ventrolateral white matter of the cervical spinal cord (40%) and the optic nerve (55%) at 1 year after tamoxifen treatment
• tamoxifen treated mice exhibit widespread CNS demyelination, peaking 5 weeks after injection and recovering by 10 weeks
• mice exhibit widespread myelin loss at 1 year after tamoxifen injection
• mice not treated with tamoxifen show some myelin loss in most CNS areas at 52 weeks of age, indicating leakiness of the cre-expressing transgene
• untreated mice exhibit about 30% fewer unmyelinated axons in the corpus callosum compared to tamoxifen treated mice

behavior/neurological
• mice show impaired motor skills starting around 40 weeks after tamoxifen injection
• tamoxifen treated mice exhibit severe ataxia starting around 40 weeks after injection
• mice exhibit seizures starting around 40 weeks after tamoxifen injection

growth/size/body
• mice show weight loss starting around 40 weeks after tamoxifen injection

hematopoietic system
• activated CD4+ T cells are present in the CNS at 10 weeks after tamoxifen injection and both activated CD4+ T cells and antigen-presenting dendritic cells are present in the CNS 40 week after tamoxifen injection

immune system
• activated CD4+ T cells are present in the CNS at 10 weeks after tamoxifen injection and both activated CD4+ T cells and antigen-presenting dendritic cells are present in the CNS 40 week after tamoxifen injection
• total numbers of CD4+ T cells, CD8+ T cells, B cells, monocytes, and dendritic cells in the CNS-draining cervical lymph nodes of tamoxifen treated mice is higher than in controls
• at 40 weeks after tamoxifen injection, autoreactive T cells capable of proliferating in response to stimulation with recombinant MOG protein are seen in the spleen and cervical lymph nodes indicating an adaptive autoimmune response against myelin
• focal lesions in tamoxifen treated mice are sites of active inflammation, frequently infiltrated by T cells, and contain a high density of microglia or macrophages
• mice show increased CD3+ T cells in the CNS as early as 7 weeks after tamoxifen injection, increased numbers of CD4+ T cells in the CNS at 10 and 40 weeks after tamoxifen injection, and increased numbers of MHCII+B7+ (CD80+CD86+) dendritic cells at 40 weeks after tamoxifen injection

Mouse Models of Human Disease
DO ID OMIM ID(s) Ref(s)
multiple sclerosis DOID:2377 OMIM:612594
OMIM:612595
OMIM:612596
J:234435




Genotype
MGI:5659978
cn17
Allelic
Composition
Gt(ROSA)26Sortm1(DTA)Jpmb/Gt(ROSA)26Sor+
Mesp1tm2(cre)Ysa/Mesp1+
Genetic
Background
involves: 129S/SvEv * C57BL/6NCrlj * CBA/JNCrlj
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Gt(ROSA)26Sortm1(DTA)Jpmb mutation (2 available); any Gt(ROSA)26Sor mutation (784 available)
Mesp1tm2(cre)Ysa mutation (1 available); any Mesp1 mutation (14 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
mortality/aging




Genotype
MGI:5289774
cn18
Allelic
Composition
Gt(ROSA)26Sortm1(DTA)Jpmb/Gt(ROSA)26Sortm1(DTA)Jpmb
Tg(KRT14-cre/ERT)20Efu/?
Genetic
Background
involves: 129S/SvEv * CD-1
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Gt(ROSA)26Sortm1(DTA)Jpmb mutation (2 available); any Gt(ROSA)26Sor mutation (784 available)
Tg(KRT14-cre/ERT)20Efu mutation (1 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
digestive/alimentary system
• treatment of mice with tamoxifen results in an expansion of Krt7-expressing cells from their ordered appearance at the squamocolumnar junction to more anterior regions of the proximal stomach; the migrating Krt7+ cells do not have squamous properties





Contributing Projects:
Mouse Genome Database (MGD), Gene Expression Database (GXD), Mouse Models of Human Cancer database (MMHCdb) (formerly Mouse Tumor Biology (MTB), Gene Ontology (GO)
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last database update
09/27/2022
MGI 6.21
The Jackson Laboratory