Phenotypes Associated with This Genotype

Genotype
MGI:6356398

• Allelic Composition: Lepr^db/Lepr^db
• Genetic Background: B6.BKS(D)-Lepr^db/JOrlRj

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

growth/size/body

increased body weight ( J:277927 )

♂ • mice exhibit increased body weight at 3 months, but not 1 month, of standard chow diet

increased susceptibility to diet-induced obesity ( J:277927 )

♂ • mice exhibit increased body weight when fed a high-calorie diet for 1 or 3 months

homeostasis/metabolism

increased susceptibility to diet-induced obesity ( J:277927 )

♂ • mice exhibit increased body weight when fed a high-calorie diet for 1 or 3 months

increased circulating ketone body level ( J:277927 )

♂ • plasma beta-hydroxybutyrate levels are greatly increased after 3 months of the high-calorie diet

increased cholesterol level ( J:277927 )

♂ • total cholesterol levels are increased in mice fed a high-calorie diet for 1 month and increased further when fed for 3 months

immune system

liver inflammation ( J:277927 )

♂ • hepatic necroinflammation is not prominent, however it is aggravated after 1 month of high-calorie diet compared to standard diet and tends to alleviate with time

♂ • non-alcoholic steatohepatitis is seen occasionally after 3 months of a standard diet and is seen in 3 of 9 mice after 3 months of the high-calorie diet

liver/biliary system

increased hepatocyte apoptosis ( J:277927 )

♂ • some hepatocyte apoptosis is seen in mice fed the standard diet and apoptosis is not increased by a high-calorie diet and even reduced after 3 months of a high-calorie diet

liver inflammation ( J:277927 )

♂ • hepatic necroinflammation is not prominent, however it is aggravated after 1 month of high-calorie diet compared to standard diet and tends to alleviate with time

♂ • non-alcoholic steatohepatitis is seen occasionally after 3 months of a standard diet and is seen in 3 of 9 mice after 3 months of the high-calorie diet

hepatic steatosis ( J:277927 )

♂ • mice develop steatosis, with steatosis mainly localized in the centrilobular and mediolobular areas; fatty change is milder than in Lep^ob homozygotes

♂ • severity of steatosis is enhanced by the high-calorie diet after 1 month, but is subsequently reduced after 3 months on this diet

macrovesicular hepatic steatosis ( J:277927 )

• macrovacuolar steatosis is similar to that seen in Lep^ob homozygotes

microvesicular hepatic steatosis ( J:277927 )

• microvesicular steatosis is more frequently seen than in Lep^ob homozygotes

liver fibrosis ( J:277927 )

♂ • some portal and perisinusoidal fibrosis is seen in standard diet fed mice at 3 months and is increased when mice are fed the high-calorie diet

cellular

increased hepatocyte apoptosis ( J:277927 )

♂ • some hepatocyte apoptosis is seen in mice fed the standard diet and apoptosis is not increased by a high-calorie diet and even reduced after 3 months of a high-calorie diet

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
metabolic dysfunction-associated steatotic liver disease		DOID:0080208	OMIM:613282 OMIM:613387	J:277927