Phenotypes Associated with This Genotype

Genotype
MGI:8190837

• Allelic Composition: Mipep^tm1.1Yhig/Mipep^tm1.1Yhig; Tg(Adipoq-cre)1Evdr/0
• Genetic Background: involves: C57BL/6J * C57BL/6N * FVB/NJ

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

adipose tissue

abnormal brown fat cell differentiation ( J:365489 )

• marker analysis indicates suppression of brown adipose differentiation

increased brown fat cell lipid droplet size ( J:365489 )

• BAT lipid droplets are enlarged

whitened brown adipose tissue morphology ( J:365489 )

• brown adipose tissue (BAT) shows loss of the typical brown appearance and more large lipid droplets are seen than in controls, indicating whitening of BAT

abnormal fat cell mitochondrial morphology ( J:365489 )

• adipocyte mitochondria are short and swollen, and cristae are absent

• donut-shaped mitochondria are seen in adipocytes

• morphological abnormalities in BAT mitochondria are not as pronounced as in WAT and cristae structure appears largely intact

decreased fat cell mitochondrial DNA content ( J:365489 )

• amount of mitochondrial DNA is lower is in gWAT and BAT, indicating decreased mitochondrial biogenesis

abnormal white adipose tissue morphology ( J:365489 )

• gonadal white adipose tissue (gWAT) is atrophic

abnormal white fat cell differentation ( J:365489 )

• small adipocyte clusters and cells exhibiting lipoblast-like characteristics are scattered throughout gWAT, indicating defective differentiation of preadipocytes into mature white adipocytes

• marker analysis indicates suppression of white adipose differentiation

decreased white adipose tissue mass ( J:365489 )

• mice have less adipose mass, particularly in subcutaneous white adipose tissue (sWAT)

• however, size of mature white adipocytes is unaltered

abnormal brown adipose tissue physiology ( J:365489 )

• marker analysis suggests that the stress response is accelerated in BAT, but not in WAT

white adipose tissue inflammation ( J:365489 )

• both CD11b+ F4/80+ cells MHCII^high CD11c^low (dominant macrophages) and MHCII^high CD11c^high (infiltrating macrophages) are increased in gWAT, indicating inflammation of WAT

cellular

abnormal brown fat cell differentiation ( J:365489 )

• marker analysis indicates suppression of brown adipose differentiation

abnormal white fat cell differentation ( J:365489 )

• small adipocyte clusters and cells exhibiting lipoblast-like characteristics are scattered throughout gWAT, indicating defective differentiation of preadipocytes into mature white adipocytes

• marker analysis indicates suppression of white adipose differentiation

abnormal fat cell mitochondrial morphology ( J:365489 )

• adipocyte mitochondria are short and swollen, and cristae are absent

• donut-shaped mitochondria are seen in adipocytes

• morphological abnormalities in BAT mitochondria are not as pronounced as in WAT and cristae structure appears largely intact

decreased fat cell mitochondrial DNA content ( J:365489 )

• amount of mitochondrial DNA is lower is in gWAT and BAT, indicating decreased mitochondrial biogenesis

growth/size/body

decreased body weight ( J:365489 )

• a significant decrease in body weight begins around 12-15 weeks of age

• however, food intake, body temperature, locomotor activity, VO2, VCO2, respiratory quotient, and energy expenditure are similar to controls

increased liver weight ( J:365489 )

increased spleen weight ( J:365489 )

hematopoietic system

increased spleen weight ( J:365489 )

increased granulocyte number ( J:365489 )

• spleen shows higher number of granulocytes

decreased T cell number ( J:365489 )

• the number of T cells is lower

• however, B cell number remains unchanged

increased macrophage cell number ( J:365489 )

• spleen shows higher number of macrophages

increased monocyte cell number ( J:365489 )

• spleen shows higher number of monocytes

homeostasis/metabolism

increased circulating glucose level ( J:365489 )

• plasma glucose is slightly, but significantly, increased

increased circulating insulin level ( J:365489 )

• basal level of plasma insulin is increased

increased circulating triglyceride level ( J:365489 )

• plasma triglycerides are slightly elevated

impaired glucose tolerance ( J:365489 )

• glucose tolerance test shows mild impairment in glucose tolerance

insulin resistance ( J:365489 )

• insulin tolerance test shows mild impairment in insulin sensitivity

increased cytokine level ( J:365489 )

• plasma levels of various cytokines are elevated at 27 weeks of age

immune system

increased spleen weight ( J:365489 )

increased granulocyte number ( J:365489 )

• spleen shows higher number of granulocytes

decreased T cell number ( J:365489 )

• the number of T cells is lower

• however, B cell number remains unchanged

increased macrophage cell number ( J:365489 )

• spleen shows higher number of macrophages

increased monocyte cell number ( J:365489 )

• spleen shows higher number of monocytes

increased cytokine level ( J:365489 )

• plasma levels of various cytokines are elevated at 27 weeks of age

increased inflammatory response ( J:365489 )

• mice show systemic inflammation

white adipose tissue inflammation ( J:365489 )

• both CD11b+ F4/80+ cells MHCII^high CD11c^low (dominant macrophages) and MHCII^high CD11c^high (infiltrating macrophages) are increased in gWAT, indicating inflammation of WAT

liver/biliary system

increased liver weight ( J:365489 )

hepatic steatosis ( J:365489 )

• mild fatty liver

mortality/aging

premature death ( J:365489 )

♂ • males exhibit a shorter lifespan

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
lipodystrophy		DOID:811		J:365489