Phenotypes Associated with This Genotype

Genotype
MGI:5471586

• Allelic Composition: Insr^tm1Khn/Insr^tm1Khn; Lepr^tm1.1Chua/Lepr^tm1.1Chua; Tg(Pomc1-cre)16Lowl/0
• Genetic Background: involves: 129 * 129S4/SvJae * 129S6/SvEvTac * C57BL/6J * FVB/N

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

adipose tissue

increased abdominal adipose tissue amount ( J:192274 )

♀ • trend towards increased intra-abdominal adiposity at 4 months of age

increased fat cell size ( J:192274 )

♀ • perigonadal adipocyte hypertrophy at 4 months of age

abnormal gonadal fat pad morphology ( J:192274 )

♀ • perigonadal adipocyte hypertrophy at 4 months of age

♀ • an increase in macrophage accumulation is seen in the perigonadal fat indicating inflammation

increased percent body fat/body weight ( J:192274 )

♀ • percent body fat is increased in females at 4 months of age, however absolute body weight is not increased at this time

white adipose tissue inflammation ( J:192274 )

♀ • an increase in macrophage accumulation is seen in the perigonadal fat, and macrophage marker analysis and cytokine expression indicates low-grade inflammation in adipose tissue

endocrine/exocrine glands

absent corpus luteum ( J:192274 )

♀ • 45% of mice lack either corpora lutea or preovulatory follicles

absent mature ovarian follicles ( J:192274 )

♀ • 45% of mice lack either corpora lutea or preovulatory follicles

ovary inflammation ( J:192274 )

♀ • low-grade inflammation as indicated by increased IL-6 expression in the ovary

growth/size/body

decreased lean body mass ( J:192274 )

♀ • percent lean body mass is decreased at 4 months of age

homeostasis/metabolism

hyperglycemia ( J:192274 )

♀ • females are hyperglycemic before (at 3 months of age) and during pregnancy (at gestational days 12 and 15), without evidence of gestational glucose intolerance

increased circulating leptin level ( J:192274 )

♀ • circulating levels of adipokine leptin are increased at 4 months of age

immune system

white adipose tissue inflammation ( J:192274 )

♀ • an increase in macrophage accumulation is seen in the perigonadal fat, and macrophage marker analysis and cytokine expression indicates low-grade inflammation in adipose tissue

ovary inflammation ( J:192274 )

♀ • low-grade inflammation as indicated by increased IL-6 expression in the ovary

liver inflammation ( J:192274 )

♀ • low-grade inflammation as indicated by increased IL-1beta expression in the liver

liver/biliary system

liver inflammation ( J:192274 )

♀ • low-grade inflammation as indicated by increased IL-1beta expression in the liver

reproductive system

absent corpus luteum ( J:192274 )

♀ • 45% of mice lack either corpora lutea or preovulatory follicles

absent mature ovarian follicles ( J:192274 )

♀ • 45% of mice lack either corpora lutea or preovulatory follicles

ovary inflammation ( J:192274 )

♀ • low-grade inflammation as indicated by increased IL-6 expression in the ovary

decreased ovulation rate ( J:192274 )

♀ • females exhibit reduced ovulation but show normal cycling suppression from fasting

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
polycystic ovary syndrome		DOID:11612	OMIM:184700	J:192274