Phenotypes Associated with This Genotype

Genotype
MGI:4358795

• Allelic Composition: Nr1h3^tm1Djm/Nr1h3^tm1Djm
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6

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

growth/size/body

enlarged ovary ( J:158168 )

♀ • following superovulation protocols, ovary size is increased compared with ovaries from similarly treated wild-type mice

♀ • however, estradiol-treated mice have normal sized ovaries

ovary cyst ( J:158168 )

♀ • superovulated-mice exhibit hemorrhagic cysts unlike similarly treated wild-type mice

increased liver weight ( J:47971 )

• 3 months on a high cholesterol diet leads to a doubling in liver mass without increasing body weight

mortality/aging

increased susceptibility to induced morbidity/mortality ( J:81696 )

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

reproductive system

increased male germ cell apoptosis ( J:120913 )

♂ • apoptosis of germ cells within seminiferous tubules is more than double that of controls

abnormal corpus luteum morphology ( J:158168 )

♀ • superovulated-mice rarely exhibit hemorrhage of the corpus luteum unlike similarly treated wild-type mice

enlarged ovary ( J:158168 )

♀ • following superovulation protocols, ovary size is increased compared with ovaries from similarly treated wild-type mice

♀ • however, estradiol-treated mice have normal sized ovaries

ovary cyst ( J:158168 )

♀ • superovulated-mice exhibit hemorrhagic cysts unlike similarly treated wild-type mice

abnormal ovary physiology ( 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

ovary hemorrhage ( J:158168 )

♀ • superovulated-mice rarely exhibit hemorrhage of the corpus luteum unlike similarly treated wild-type mice

abnormal superovulation ( 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

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:243753 )

♀N • when fed Western diet

♀N • circulating triglyceride level

♀N • liver triglyceride level

♀N • circulating free fatty acid level

♀N • liver free fatty acid level

♀N • circulating cholesterol level both total and free

decreased circulating testosterone level ( J:120913 )

• testosterone production in the testes is significantly reduced compared to controls

increased circulating estradiol level ( J:158168 )

• superovulated-mice compared to in similarly treated wild-type

decreased circulating luteinizing hormone level ( J:120913 )

• plasma LH levels are almost half that of controls

increased circulating cholesterol level ( J:47971 )

• 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

increased circulating LDL cholesterol level ( J:47971 )

• serum LDL levels are increased 5-fold in mice that are fed a high cholesterol diet

increased circulating alanine transaminase level ( J:47971 )

• serum alanine transaminase levels are increased in mice that are fed a high cholesterol diet

increased circulating aspartate transaminase level ( J:47971 )

• serum aspartate transaminase levels are increased in mice that are fed a high cholesterol diet

increased erythrocyte sedimentation rate ( J:158168 )

• following superovulation protocols, mice exhibit an increase in blood sediment rate compared with wild-type mice indicating inflammation

abnormal bile salt homeostasis ( J:47971 )

• 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

increased liver cholesterol level ( J:47971 , J:243753 )

• 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 (J:47971)

• when fed an intermediate (0.2%) cholesterol diet, mice have increases of 3- and 10- fold after 7 and 22 days on the diet (J:47971)

♀ • both total and free when fed Western diet (J:243753)

liver/biliary system

increased liver weight ( J:47971 )

• 3 months on a high cholesterol diet leads to a doubling in liver mass without increasing body weight

increased liver cholesterol level ( J:47971 , J:243753 )

• 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 (J:47971)

• when fed an intermediate (0.2%) cholesterol diet, mice have increases of 3- and 10- fold after 7 and 22 days on the diet (J:47971)

♀ • both total and free when fed Western diet (J:243753)

hepatic steatosis ( J:47971 )

• 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

liver degeneration ( J:47971 )

• 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

pale liver ( J:47971 )

• liver appears white after 3 months on a high cholesterol diet due to presence of cholesterol filled droplets

cardiovascular system

ovary hemorrhage ( J:158168 )

♀ • superovulated-mice rarely exhibit hemorrhage of the corpus luteum unlike similarly treated wild-type mice

increased vascular permeability ( J:158168 )

• in the ovaries of superovulated-mice compared to in similarly treated wild-type

immune system

increased inflammatory response ( J:158168 )

• following superovulation protocols, mice exhibit an increase in blood sediment rate compared with wild-type mice indicating inflammation

increased susceptibility to bacterial infection ( J:81696 )

• 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

abnormal corpus luteum morphology ( J:158168 )

♀ • superovulated-mice rarely exhibit hemorrhage of the corpus luteum unlike similarly treated wild-type mice

enlarged ovary ( J:158168 )

♀ • following superovulation protocols, ovary size is increased compared with ovaries from similarly treated wild-type mice

♀ • however, estradiol-treated mice have normal sized ovaries

ovary cyst ( J:158168 )

♀ • superovulated-mice exhibit hemorrhagic cysts unlike similarly treated wild-type mice

abnormal ovary physiology ( 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

ovary hemorrhage ( J:158168 )

♀ • superovulated-mice rarely exhibit hemorrhage of the corpus luteum unlike similarly treated wild-type mice

cellular

increased male germ cell apoptosis ( J:120913 )

♂ • apoptosis of germ cells within seminiferous tubules is more than double that of controls

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
ovarian hyperstimulation syndrome		DOID:5425	OMIM:608115	J:158168