Mouse Genome Informatics
tg
    Tg(aP2-SREBF1c)9884Reh/0
involves: C57BL/6J * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
       
mortality/aging
• ~20% of mice fail to thrive and die within the first 3 weeks of life

growth/size/body
• mice appear slightly runted during the first week of life
• although most mice consuming a chow diet gain weight and reach a similar weight to that of control littermates by P40, a few remain runted throughout life
• during the first week of life mice exhibit a distended abdomen due to liver enlargement

adipose tissue
N
• despite adipose tissue defects, adipogenesis is normal in embryonic fibroblasts (J:125992)
• brown fat is hypertrophic and contains fat-laden cells that resemble immature white fat
• at P7, mice display enlarged interscapular and submandibular brown fat depots relative to control mice
• at P8, the cytoplasm of mutant brown adipocytes displays large unilocular vacuoles similar to those of immature white adipocytes but unlike the small multilocular vacuoles observed in wild-type brown adipocytes
• at P40, most mutant brown adipocytes contain a prominent unilocular fat droplet
• at P8, mutant brown adipocytes are dramatically enlarged and stain palely
• at P40, most mutant brown adipocytes remain significantly enlarged
• at P8, the mutant epididymal fat pad consists predominantly of small immature adipocytes with brightly eosinophilic cytoplasm and a distinct unilocular vacuole
• at P40, the mutant epididymal white fat contains a mixture of mature and immature adipocytes with significant size heterogeneity; immature adipocytes with bright eosinophilic cytoplasm, a round nucleus, and a distinct unilocular vacuole are observed
• at P40, some epididymal fat pads exhibit histological evidence of mild inflammation and fibrosis
• at 12 weeks of age, the mutant epididymal fat pad weighs only ~35% of the wild-type fat pad (160 mg versus 510 mg, respectively)
• at P7, all mice exhibit enlarged interscapular brown fat pads, manifested as bilobed interscapular humps
• at 7-12 weeks of age, mutant interscapular fat pads appear significantly enlarged, very firm, and white
• at P40, mutant interscapular brown fat consists of enlarged adipocytes containing large unilocular fat droplets; the interstitium shows signs of mild chronic inflammation
• at 12 weeks of age, mutant interscapular fat weighs nearly twice as much as wild-type (110 mg versus 58 mg, respectively)
• white fat fails to differentiate fully, and the size of white fat depots is significantly reduced
• at 7-12 weeks of age, mutant white adipose tissue is atrophic
• at P40, epididymal, omental and perinephric white fat deposits are significantly reduced

homeostasis/metabolism
• mice exhibit a significant increase in nonfasting plasma glucose levels, with a mean value 305 mg/dl
• mice exhibit a 60-fold increase in nonfasting plasma insulin levels relative to control littermates
• at 7 weeks of age, plasma cholesterol levels are mildly, but significantly, increased
• at 7 weeks of age, plasma triglyceride levels are mildly, but significantly, increased
• at 9-11 months of age, plasma triglyceride levels are significantly higher (mean of 450 mg/dl; range, 367-565) than those of control littermates (mean of 97 mg/dl; range, 75-147)
• all mice are significantly resistant to the glucose-lowering effect of exogenous insulin
• however, there is no evidence for insulin resistance in skeletal muscle
• at 7 weeks of age, the hepatic content of triglycerides is significantly increased

liver/biliary system
• at 7 weeks of age, the hepatic content of triglycerides is significantly increased
• at P8, mutant livers display uniform vacuolar changes throughout the hepatic lobule
• at P8, mutant hepatocytes are dramatically swollen; the cytoplasm stains palely eosinophilic and contains numerous microvesicular vacuoles which, in rare cases, coalesce to form a unilocular vacuole that displaces the nucleus peripherally
• at P40, hepatocellular swelling is less severe than at P8, and it is confined to the centrolobular zone; no hepatitis or fibrosis is observed
• at P7, mutant livers are massively enlarged
• mutant livers remain enlarged at 7-12 weeks of age
• at 12 weeks of age, mutant liver weighs twice as much as wild-type liver (3.9 g versus 1.5 g, respectively)
• as early as P8, mutant livers are overloaded with fat
• despite a markedly fatty liver, plasma levels of albumin, aspartate aminotransferase, and bilirubin remain normal at 7 weeks of age
• at P7, mutant livers are markedly pale
• mutant livers remain pale at 7-12 weeks of age

endocrine/exocrine glands
• at 7-12 weeks of age, mutant pancreata are significantly enlarged

hematopoietic system
• at 7-12 weeks of age, mutant spleens are significantly enlarged

immune system
• at 7-12 weeks of age, mutant spleens are significantly enlarged
• at 7-12 weeks of age, mutant abdominal lymph nodes are significantly enlarged

Mouse Models of Human Disease
OMIM IDRef(s)
Diabetes Mellitus, Noninsulin-Dependent; NIDDM 125853 J:50770
Lipodystrophy, Congenital Generalized, Type 2; CGL2 269700 J:50770