Phenotypes Associated with This Genotype

Genotype
MGI:5515728

• Allelic Composition: Tyk2^tm1Shmd/Tyk2^tm1Shmd
• Genetic Background: either: (involves: 129 * 129P2/OlaHsd) or (involves: 129P2/OlaHsd * C57BL/6)

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

adipose tissue

abnormal brown adipose tissue morphology ( J:195099 )

♂ • marker analysis indicates abnormal brown adipose tissue (BAT) development

♂ • BAT cells contain large unilocular fat droplets compared to multilocular fat droplets in wild-type BAT

abnormal fat cell differentiation ( J:195099 )

♂ • preadiopocytes do not differentiate

cellular

abnormal fat cell differentiation ( J:195099 )

♂ • preadiopocytes do not differentiate

disorganized mitochondrial cristae ( J:195099 )

♂ • mitochondria of BAT and skeletal muscle, but not in the heart, shows disorganized cristae

abnormal mitochondrial physiology ( J:195099 )

♂ • oxygen consumption is decreased in mitochondria when pyruvate and malate are used as substrates for complex I activity and succinate for complex II activity

♂ • addition of GDP decreases oxygen consumption in wild-type but not mutant mitochondria

growth/size/body

increased body weight ( J:195099 )

♂ • increase in body weight is seen as early as 12-16 weeks of age on a normal chow diet

obese ( J:195099 )

♂ • by 12 months of age, mutants are about 20 grams heavier than wild-type mice

♂ • however, mutants exhibit normal food intake and physical activity

homeostasis/metabolism

impaired adaptive thermogenesis ( J:195099 )

♂ • body temperatures are lower in mutants than controls when exposed to 4 degrees C for 12 hours

increased circulating insulin level ( J:195099 )

♂

increased circulating free fatty acids level ( J:195099 )

♂

abnormal body temperature homeostasis ( J:195099 )

♂ • produce 20% less heat during both day and night cycles

decreased energy expenditure ( J:195099 )

♂

impaired glucose tolerance ( J:195099 )

♂ • abnormal glucose clearance suggestive of insulin resistance

increased cholesterol level ( J:195099 )

♂

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
obesity		DOID:9970	OMIM:601665	J:195099