Tg(aP2-SREBF1c)9884Reh Transgene Detail MGI Mouse (MGI:3028848)

Tg(aP2-SREBF1c)9884Reh
Transgene Detail

Nomenclature

Symbol:	Tg(aP2-SREBF1c)9884Reh
Name:	transgene insertion 9884, Robert E Hammer
MGI ID:	MGI:3028848
Synonyms:	aP2-SREBP-1c436
Transgene:	Tg(aP2-SREBF1c)9884Reh Location: unknown

Transgene
origin

Strain of Origin:

(C57BL/6J x SJL)F2

Transgene
description

Transgene Type:	Transgenic (random, expressed)
Mutation:	Insertion
	Sequence encoding residues 1 through 436 of human nuclear sterol regulatory element binding protein-1c (SREBF1c) was adjoined to 5.4 kb of the mouse adipose-specific enhancer/promoter of aP2. SREBF1c sequence encoding the membrane-attachment domain was not included in the construct, permitting the expressed componen to enter the nucleus without a requirement for proteolysis. (J:50770)

Find Mice (IMSR)

Mouse strains and cell lines available from the International Mouse Strain Resource (IMSR)

Carrying this Mutation:

Mouse Strains: 1 strain available Cell Lines: 0 lines available

Phenotype
summary

Phenotype Summary by Mammalian Phenotype terms

(show or hide all annotated terms)

Genotypes are listed in the next section.

Key:

hm	homozygous	ht	heterozygous
cn	conditional genotype	cx	complex: > 1 genome feature
tg	involves transgenes	ot	other: hemizygous, indeterminate,...
N	normal phenotype		expected model not found

Affected Systems	Genotypes:	tg1
adipose tissue		√
adipose tissue phenotype		N
abnormal brown adipose tissue morphology		√
increased brown adipose tissue amount		√
abnormal brown fat cell morphology		√
increased brown fat cell lipid droplet size		√
increased brown fat cell size		√
abnormal epididymal fat pad morphology		√
decreased epididymal fat pad weight		√
abnormal interscapular fat pad morphology		√
increased interscapular fat pad weight		√
abnormal white adipose tissue morphology		√
decreased white adipose tissue amount		√
		tg1
digestive/alimentary system		√
enlarged pancreas		√
		tg1
endocrine/exocrine glands		√
enlarged pancreas		√
		tg1
growth/size		√
decreased body size		√
distended abdomen		√
		tg1
hematopoietic system		√
enlarged spleen		√
		tg1
homeostasis/metabolism		√
hyperglycemia		√
increased circulating insulin level		√
increased circulating cholesterol level		√
increased circulating triglyceride level		√
insulin resistance		√
increased liver triglyceride level		√
		tg1
immune system		√
enlarged spleen		√
abnormal abdominal lymph node morphology		√
		tg1
lethality/postnatal		√
postnatal lethality		√
		tg1
liver/biliary system		√
abnormal liver lobule morphology		√
abnormal hepatocyte morphology		√
enlarged liver		√
increased liver weight		√
hepatic steatosis		√
pale liver		√

		tg1
Disease Models		√
Diabetes Mellitus, Noninsulin-Dependent; NIDDM		√
Lipodystrophy, Congenital Generalized, Type 2; CGL2		√

Phenotypic
data by
genotype

Phenotypic Data by Genotype

(show or hide all phenotypic details)

Genotype

Allelic Composition

Genetic Background

tg1 Disease Model

Tg(aP2-SREBF1c)9884Reh/0

involves: C57BL/6J * SJL

lethality/postnatalpostnatal lethality (J:50770)

~20% of mice fail to thrive and die within the first 3 weeks of life

growth/sizedecreased body size (J:50770)

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

distended abdomen (J:50770)

during the first week of life mice exhibit a distended abdomen due to liver enlargement

adipose tissueadipose tissue phenotype (J:125992)

despite adipose tissue defects, adipogenesis is normal in embryonic fibroblasts

abnormal brown adipose tissue morphology (J:50770)

brown fat is hypertrophic and contains fat-laden cells that resemble immature white fat

increased brown adipose tissue amount (J:50770)

at P7, mice display enlarged interscapular and submandibular brown fat depots relative to control mice

abnormal brown fat cell morphology (J:50770)

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

increased brown fat cell lipid droplet size (J:50770)

at P40, most mutant brown adipocytes contain a prominent unilocular fat droplet

increased brown fat cell size (J:50770)

at P8, mutant brown adipocytes are dramatically enlarged and stain palely

at P40, most mutant brown adipocytes remain significantly enlarged

abnormal epididymal fat pad morphology (J:50770)

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

decreased epididymal fat pad weight (J:50770)

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)

abnormal interscapular fat pad morphology (J:50770)

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

increased interscapular fat pad weight (J:50770)

at 12 weeks of age, mutant interscapular fat weighs nearly twice as much as wild-type (110 mg versus 58 mg, respectively)

abnormal white adipose tissue morphology (J:50770)

white fat fails to differentiate fully, and the size of white fat depots is significantly reduced

decreased white adipose tissue amount (J:50770)

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/metabolismhyperglycemia (J:50770)

mice exhibit a significant increase in nonfasting plasma glucose levels, with a mean value 305 mg/dl

increased circulating insulin level (J:50770)

mice exhibit a 60-fold increase in nonfasting plasma insulin levels relative to control littermates

increased circulating cholesterol level (J:50770)

at 7 weeks of age, plasma cholesterol levels are mildly, but significantly, increased

increased circulating triglyceride level (J:50770)

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)

insulin resistance (J:50770)

all mice are significantly resistant to the glucose-lowering effect of exogenous insulin

however, there is no evidence for insulin resistance in skeletal muscle

increased liver triglyceride level (J:50770)

at 7 weeks of age, the hepatic content of triglycerides is significantly increased

liver/biliary systemabnormal liver lobule morphology (J:50770)

at P8, mutant livers display uniform vacuolar changes throughout the hepatic lobule

abnormal hepatocyte morphology (J:50770)

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

enlarged liver (J:50770)

at P7, mutant livers are massively enlarged

mutant livers remain enlarged at 7-12 weeks of age

increased liver weight (J:50770)

at 12 weeks of age, mutant liver weighs twice as much as wild-type liver (3.9 g versus 1.5 g, respectively)

hepatic steatosis (J:50770)

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

pale liver (J:50770)

at P7, mutant livers are markedly pale

mutant livers remain pale at 7-12 weeks of age

digestive/alimentary systemenlarged pancreas (J:50770)

at 7-12 weeks of age, mutant pancreata are significantly enlarged

endocrine/exocrine glandsenlarged pancreas (J:50770)

at 7-12 weeks of age, mutant pancreata are significantly enlarged

hematopoietic systemenlarged spleen (J:50770)

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

immune systemenlarged spleen (J:50770)

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

abnormal abdominal lymph node morphology (J:50770)

at 7-12 weeks of age, mutant abdominal lymph nodes are significantly enlarged

Mouse Models of Human Disease	Note	Ref(s)
Models involving transgenes or other mutation types.¹
Diabetes Mellitus, Noninsulin-Dependent; NIDDM		J:50770
Lipodystrophy, Congenital Generalized, Type 2; CGL2		J:50770

¹Models involving transgenes or other mutation types may also appear in other sections of the table.

Disease
models

Mouse Models of Human Disease	Note	Genotype			Ref(s)
			Allelic Composition	Genetic Background
Models involving transgenes or other mutation types.¹
Diabetes Mellitus, Noninsulin-Dependent; NIDDM OMIM ID: 125853		tg1	Tg(aP2-SREBF1c)9884Reh/0	involves: C57BL/6J * SJL	J:50770
Lipodystrophy, Congenital Generalized, Type 2; CGL2 OMIM ID: 269700		tg1	Tg(aP2-SREBF1c)9884Reh/0	involves: C57BL/6J * SJL	J:50770

¹Models involving transgenes or other mutation types may also appear in other sections of the table.

Notes

This line was generated from founder number 988-4.

References

Original:	J:50770 Shimomura I et al., "Insulin resistance and diabetes mellitus in transgenic mice expressing nuclear SREBP-1c in adipose tissue: model for congenital generalized lipodystrophy." Genes Dev 1998 Oct 15;12(20):3182-94
All:	8 reference(s)

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