Phenotypes associated with this allele

• Allele Symbol: Tyk2^tm1Shmd
• Allele Name: targeted mutation 1, Kazuya Shimoda
• Allele ID: MGI:2389582
• Summary: 3 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Tyk2^tm1Shmd/Tyk2^tm1Shmd	either: (involves: 129 * 129P2/OlaHsd) or (involves: 129P2/OlaHsd * C57BL/6)	MGI:5515728
hm2	Tyk2^tm1Shmd/Tyk2^tm1Shmd	involves: 129P2/OlaHsd	MGI:2654835
cn3	Gt(ROSA)26Sor^tm1(Stat3*A661C*N663C)Sbkv/? Tg(Fabp4-cre/ERT2)1Ipc/0 Tyk2^tm1Shmd/Tyk2^tm1Shmd	involves: 129P2/OlaHsd * C57BL/6 * SJL	MGI:5515733

Genotype
MGI:5515728

hm1

• 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

Genotype
MGI:2654835

hm2

• Allelic Composition: Tyk2^tm1Shmd/Tyk2^tm1Shmd
• Genetic Background: involves: 129P2/OlaHsd

hematopoietic system

abnormal common myeloid progenitor cell morphology ( J:109408 )

• interferon-gamma growth suppression of colony-forming units granulocyte-macrophage and basal burst-forming unit-erythroid from bone marrow cells and T-depleted bone marrow cells is impaired

abnormal T cell differentiation ( J:65409 )

• naive helper T cells exhibit impaired differentiation into Th1 cells

abnormal T cell physiology ( J:65409 )

• defective interleukin-12 mediated T cell function

abnormal splenocyte physiology ( J:65409 )

• splenocytes do not respond to a small amount of IFN-alpha, although they do to high concentrations

cellular

abnormal cell cycle ( J:109408 )

• upon treatment with interferon-gamma, normal S-phase accumulation of bone marrow cells fails to occur

immune system

abnormal T cell differentiation ( J:65409 )

• naive helper T cells exhibit impaired differentiation into Th1 cells

abnormal T cell physiology ( J:65409 )

• defective interleukin-12 mediated T cell function

abnormal splenocyte physiology ( J:65409 )

• splenocytes do not respond to a small amount of IFN-alpha, although they do to high concentrations

decreased interferon-gamma secretion ( J:65409 )

• stimulation of spleens cells with IL-12 results in no IFN-gamma production as observed in wild-type, however numbers of T and NK cells are normal

Genotype
MGI:5515733

cn3

• Allelic Composition: Gt(ROSA)26Sor^{tm1(Stat3*A661C*N663C)Sbkv}/?; Tg(Fabp4-cre/ERT2)1Ipc/0; Tyk2^tm1Shmd/Tyk2^tm1Shmd
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6 * SJL

adipose tissue

adipose tissue phenotype ( J:195099 )

♂N • mice exhibit normal brown adipose tissue morphology with reduced body weight compared to single Tyk2 homozygotes

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:195099 )

♂N • mice exhibit improved insulin sensitivity compared to single Tyk2 homozygotes