Mouse Genome Informatics
hm1
    Nr1h2tm1Djm/Nr1h2tm1Djm
involves: 129S6/SvEvTac
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
integument
• the epidermis of mutant mice is thinner with fewer proliferating cells in the basal layer compared to wild-type littermates
• treatment with oxysterol does not result in thickening of the epidermis unlike in wild-type littermates and Nr1h3tm1Djm homozygotes


Mouse Genome Informatics
hm2
    Nr1h2tm1Djm/Nr1h2tm1Djm
involves: 129S6/SvEvTac * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• mice succumb to infection of Listeria monocytogenes 2-3 days earlier than controls
• occasionally mothers fail to expulse pups from uterine horns leading rarely to death

immune system
• mice succumb to infection of Listeria monocytogenes 2-3 days earlier than controls

reproductive system
• proliferation of male germ cells is significantly decreased compared to controls (J:120913)
• Sertoli cells have vacuoles containing cholesterol esters (J:120913)
• vacuoles filled with cholesterol esters are present within the myoctes (J:120923)
• concentration of cholesterol esters are about 25-fold higher at 3 and 12 months of age (J:120923)
• occasionally mothers fail to expulse pups from uterine horns leading to hind-limb paralysis and rarely to death (J:120923)
• myometrium muscle has lower amplitudes of contraction compared to controls in response to pharmacological levels of oxytocin (J:120923)

endocrine/exocrine glands
• Sertoli cells have vacuoles containing cholesterol esters (J:120913)

behavior/neurological
• occasionally mothers fail to expulse pups from uterine horns leading to hind-limb paralysis and rarely to death

muscle
• myometrium (uterus) muscle has lower amplitudes of contraction compared to controls in response to pharmacological levels of oxytocin

cellular
• proliferation of male germ cells is significantly decreased compared to controls (J:120913)


Mouse Genome Informatics
cx3
    Nr1h2tm1Djm/Nr1h2tm1Djm
Nr1h3tm1Djm/Nr1h3tm1Djm

involves: 129S6/SvEvTac
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
homeostasis/metabolism
• hepatic cholesterol levels are 4-fold higher than controls in mice fed a 0.2% cholesterol diet

liver/biliary system
• hepatic cholesterol levels are 4-fold higher than controls in mice fed a 0.2% cholesterol diet


Mouse Genome Informatics
cx4
    Npc1m1N/Npc1m1N
Nr1h2tm1Djm/Nr1h2tm1Djm

involves: 129S6/SvEvTac * BALB/c
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• mice die between 60 and 90 days of age from neurodegenerative disease, which is significantly faster than Npc1 mutants on a wild-type background

Mouse Models of Human Disease
OMIM IDRef(s)
Niemann-Pick Disease, Type C1; NPC1 257220 J:130969


Mouse Genome Informatics
cx5
    Nr1h2tm1Djm/Nr1h2tm1Djm
Tg(APPswe,PSEN1dE9)85Dbo/0

involves: 129S6/SvEvTac * C3H * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
• a significant increase in cortical the Abeta1-40 plaque number is seen in mice at 32 weeks of age compared transgenic mice on a wild-type background
• plaques are also increased in size
• there is also a significant increase in Abeta1-42 plaque number at this age

homeostasis/metabolism
• a significant increase in cortical the Abeta1-40 plaque number is seen in mice at 32 weeks of age compared transgenic mice on a wild-type background
• plaques are also increased in size
• there is also a significant increase in Abeta1-42 plaque number at this age


Mouse Genome Informatics
cx6
    Nr1h2tm1Djm/Nr1h2tm1Djm
Nr1h3tm1Djm/Nr1h3tm1Djm

involves: 129S6/SvEvTac * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• all mice die when given 104 CFU of Listeria monocytogenes compared to all wild-type controls surviving
• at higher doses mice succumb to the infection 2-3 days earlier than controls
• occasionally mothers fail to expulse pups from uterine horns leading rarely to death

reproductive system
• proliferation of male germ cells is significantly decreased compared to controls (J:120913)
• vacuoles filled with cholesterol esters are present within the myoctes (J:120923)
• concentration of cholesterol esters are 32-fold higher at 3 months of age and 66-fold higher at 12 months of age (J:120923)
• 20-30% of 5.5 month old males have abnormal tubules with cellular aggregates clumping in the middle without any spermatozoa (J:120913)
• by 10 months of age, most tubules are empty without any spermatozoa (J:120913)
• Leydig cells in mice 3.5 months of age are enlarged (J:120913)
• Sertoli cells have vacuoles filled with cholesterol esters within in them (J:120913)
• by 12 months of age, seminiferous tubules are degraded from deposits cholesterol (J:120913)
• a significant decline in testis weight is noted starting at 9 weeks of age (J:120913)
• as mice age, testis lose weight and morphology of the glands becomes becomes disrupted by cholesterol deposits (J:120913)
• occasionally mothers fail to expulse pups from uterine horns leading to hind-limb paralysis and rarely to death (J:120923)
• myometrium muscle has lower amplitudes of contraction compared to controls in response to pharmacological levels of oxytocin (J:120923)
• apoptosis of germ cells within seminiferous tubules is more than double that of controls (J:120913)
• ratio of proliferating/apoptotic male germ cells is significantly decreased compared to controls (J:120913)
• male mice start exhibiting fertility problems around 5 months of age with complete loss of fertility occurring by 7 months of age (J:120913)
• the fertility problems exhibited at 5 months of age include only 55% of mated females exhibiting vaginal plugs and dramatic reductions in litter size (J:120913)

homeostasis/metabolism
• testosterone production in the testes is significantly reduced compared to controls
• plasma LH levels are almost half that of controls

behavior/neurological
• occasionally mothers fail to expulse pups from uterine horns leading to hind-limb paralysis and rarely to death

immune system
• peritoneal macrophages have a 2.7-fold increase in free cholesterol and a 2.4-fold increase in total cholesterol
• all mice die when given 104 CFU of Listeria monocytogenes compared to all wild-type controls surviving
• at higher doses mice succumb to the infection 2-3 days earlier than controls

muscle
• myometrium (uterus) muscle has lower amplitudes of contraction compared to controls in response to pharmacological levels of oxytocin

hematopoietic system
• peritoneal macrophages have a 2.7-fold increase in free cholesterol and a 2.4-fold increase in total cholesterol
• when bone marrow is transferred into irradiated Apoe-null mice, bone marrow cells fail to lower total serum cholesterol levels as wild-type bone marrow cells do
• aortas from these mice have 3- to 8-fold more atherosclerotic lesions than Apoe-null mice receiving wild-type bone marrow
• increased atherosclerotic lesions are also observed when mutant bone marrow is transferred into LDLR-null mice
• spleens of recipient LDLR-null mice are also enlarged

endocrine/exocrine glands
• 20-30% of 5.5 month old males have abnormal tubules with cellular aggregates clumping in the middle without any spermatozoa (J:120913)
• by 10 months of age, most tubules are empty without any spermatozoa (J:120913)
• Leydig cells in mice 3.5 months of age are enlarged (J:120913)
• Sertoli cells have vacuoles filled with cholesterol esters within in them (J:120913)
• by 12 months of age, seminiferous tubules are degraded from deposits cholesterol (J:120913)
• a significant decline in testis weight is noted starting at 9 weeks of age (J:120913)
• as mice age, testis lose weight and morphology of the glands becomes becomes disrupted by cholesterol deposits (J:120913)

cellular
• apoptosis of germ cells within seminiferous tubules is more than double that of controls (J:120913)
• ratio of proliferating/apoptotic male germ cells is significantly decreased compared to controls (J:120913)
• proliferation of male germ cells is significantly decreased compared to controls (J:120913)