Mouse Genome Informatics
hm1
    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
• mice succumb to infection of Listeria monocytogenes 2-3 days earlier than controls

reproductive system
• apoptosis of germ cells within seminiferous tubules is more than double that of controls (J:120913)
• superovulated-mice rarely exhibit hemorrhage of the corpus luteum unlike similarly treated wild-type mice (J:158168)
• following superovulation protocols, ovary size is increased compared with ovaries from similarly treated wild-type mice (J:158168)
• however, estradiol-treated mice have normal sized ovaries (J:158168)
• superovulated-mice exhibit hemorrhagic cysts unlike similarly treated wild-type mice (J:158168)
• following follicle retrieval, a greater number of follicles are expulsed with 45% dead oocytes or empty zonae pellucidae unlike in similarly treated wild-type mice (J:158168)
• superovulated-mice rarely exhibit hemorrhage of the corpus luteum unlike similarly treated wild-type mice (J:158168)
• superovulated-mice exhibit increased follicle expulsion, increased number of dead oocytes or empty zona pellucida, enlarged ovaries, ovarian cysts, rare ovarian hemorrhage, increased ovarian vascular permeability, circulating estradiol, and inflammation compared with similarly treated wild-type mice (J:158168)

homeostasis/metabolism
• testosterone production in the testes is significantly reduced compared to controls
• superovulated-mice compared to in similarly treated wild-type
• plasma LH levels are almost half that of controls
• there is a 15- to 20- fold increase in liver cholesterol levels 7 days after being switched to a high (2%) cholesterol diet while only a modest increase is observed in control mice
• when fed an intermediate (0.2%) cholesterol diet, mice have increases of 3- and 10- fold after 7 and 22 days on the diet
• serum LDL levels are increased 5-fold in mice that are fed a high cholesterol diet
• serum alanine transaminase levels are increased in mice that are fed a high cholesterol diet
• serum aspartate transaminase levels are increased in mice that are fed a high cholesterol diet
• mice fail to increase their pool of bile acid in response to a high cholesterol diet as wild-type mice do
• less fecal excretion of bile acid occurs in mice fed the high cholesterol diet compared to control mice
• the ratio of cholic acid to muricholic acid within the bile acid pool is significantly higher than controls on a chow-fed diet, and does not decrease when fed a high cholesterol diet
• there is a 15- to 20- fold increase in liver cholesterol levels 7 days after being switched to a high (2%) cholesterol diet while only a modest increase is observed in control mice
• when fed an intermediate (0.2%) cholesterol diet, mice have increases of 3- and 10- fold after 7 and 22 days on the diet

liver/biliary system
• there is a 15- to 20- fold increase in liver cholesterol levels 7 days after being switched to a high (2%) cholesterol diet while only a modest increase is observed in control mice
• when fed an intermediate (0.2%) cholesterol diet, mice have increases of 3- and 10- fold after 7 and 22 days on the diet
• 3 months on a high cholesterol diet leads to a doubling in liver mass without increasing body weight
• on high (2%) cholesterol diets, livers develop fatty deposits that increase in number and size with time while control mice exhibit no abnormalities
• the liver appears pale and is double in size, inflammatory foci are developing, and signs of liver degeneration are evident after 3 months on the diet
• signs of liver degeneration are evident after 3 months on a high cholesterol diet
• increased serum levels of alanine and aspartate amino transferases are also indicitave of liver injury
• hepatocytes have lost most of their normal cell structure after 90 days on a high cholesterol diet
• liver appears white after 3 months on a high cholesterol diet due to presence of cholesterol filled droplets

cardiovascular system
• superovulated-mice rarely exhibit hemorrhage of the corpus luteum unlike similarly treated wild-type mice (J:158168)
• in the ovaries of superovulated-mice compared to in similarly treated wild-type

immune system
• following superovulation protocols, mice exhibit an increase in blood sediment rate compared with wild-type mice indicating inflammation
• mice succumb to infection of Listeria monocytogenes 2-3 days earlier than controls
• bacterial burden in the liver of day 2 of infection is 2 logs higher than controls

endocrine/exocrine glands
• superovulated-mice rarely exhibit hemorrhage of the corpus luteum unlike similarly treated wild-type mice (J:158168)
• following superovulation protocols, ovary size is increased compared with ovaries from similarly treated wild-type mice (J:158168)
• however, estradiol-treated mice have normal sized ovaries (J:158168)
• superovulated-mice exhibit hemorrhagic cysts unlike similarly treated wild-type mice (J:158168)
• following follicle retrieval, a greater number of follicles are expulsed with 45% dead oocytes or empty zonae pellucidae unlike in similarly treated wild-type mice (J:158168)
• superovulated-mice rarely exhibit hemorrhage of the corpus luteum unlike similarly treated wild-type mice (J:158168)

cellular
• apoptosis of germ cells within seminiferous tubules is more than double that of controls (J:120913)

Mouse Models of Human Disease
OMIM IDRef(s)
Ovarian Hyperstimulation Syndrome 608115 J:158168


Mouse Genome Informatics
cx2
    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
cx3
    Nr1h3tm1Djm/Nr1h3tm1Djm
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

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


Mouse Genome Informatics
cx4
    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)