Tg(AZIP/F)1Vsn Transgene Detail MGI Mouse (MGI:3497939)

Tg(AZIP/F)1Vsn
Transgene Detail

Nomenclature

Symbol:	Tg(AZIP/F)1Vsn
Name:	transgene insertion 1, Charles Vinson
MGI ID:	MGI:3497939
Synonyms:	A-ZIP/F-1, A-ZIP/F1
Transgene:	Tg(AZIP/F)1Vsn Location: unknown

Transgene
origin

Strain of Origin:

FVB/N

Transgene
description

Transgene Type:	Transgenic (random, expressed)
Mutation:	Insertion
	A 7.6 kb segment of the Fabp4 enhancer/promoter was used to drive expression of an artificially constructed cDNA encoding a dominant-negative protein to inhibit the DNA binding of both Cebpa and Jun family members. The protein is 104 amino acids long, with an amino-terminal 9 amino acid Flag epitope, a 13 amino acid linker, a 21 amino acid designed acidic amphipathic helix and a 61 amino acid designed leucine zipper (ZIP/F). The transgene also had an SV40 intron and a PolyA signal. (J:50807)

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	tg2	tg3	tg4
adipose tissue			√
decreased brown adipose tissue amount			√
decreased white adipose tissue amount			√
		tg1	tg2	tg3	tg4
behavior/neurological			√
polydipsia			√
		tg1	tg2	tg3	tg4
digestive/alimentary system		√	√
increased pancreatic beta cell mass		√
abnormal pancreatic beta cell physiology		√
increased insulin secretion		√
pancreatic islet hyperplasia			√
		tg1	tg2	tg3	tg4
endocrine/exocrine glands		√	√
increased pancreatic beta cell mass		√
abnormal pancreatic beta cell physiology		√
increased insulin secretion		√
pancreatic islet hyperplasia			√
		tg1	tg2	tg3	tg4
growth/size		√	√
decreased body weight		√
decreased body mass index		√
weight loss			√
increased body weight			√
postnatal growth retardation			√
		tg1	tg2	tg3	tg4
homeostasis/metabolism		√	√	√	√
decreased circulating leptin level			√
abnormal glucose homeostasis			√
decreased circulating glucose level		√
increased circulating insulin level		√	√	√	√
hyperglycemia			√
abnormal lipid homeostasis			√
increased circulating free fatty acid level			√
increased triglyceride level			√
increased circulating triglyceride level			√
increased sensitivity to xenobiotic induced morbidity/mortality			√
		tg1	tg2	tg3	tg4
lethality/postnatal			√
postnatal lethality			√
		tg1	tg2	tg3	tg4
life span/aging			√
increased sensitivity to xenobiotic induced morbidity/mortality			√
premature death			√
		tg1	tg2	tg3	tg4
liver/biliary system			√
increased liver weight			√
hepatic steatosis			√
		tg1	tg2	tg3	tg4
renal/urinary system			√
polyuria			√
		tg1	tg2	tg3	tg4
reproductive system			√
reduced female fertility			√
reduced male fertility			√
		tg1	tg2	tg3	tg4
respiratory system			√
abnormal lung morphology			√
		tg1	tg2	tg3	tg4
skin/coat/nails			√
rough hair			√

Phenotypic
data by
genotype

Phenotypic Data by Genotype

(show or hide all phenotypic details)

Genotype	Allelic Composition	Genetic Background
tg1	Tg(AZIP/F)1Vsn/0	FVB-Tg(AZIP/F)1Vsn/J
homeostasis/metabolism decreased circulating glucose level (J:145998) increased circulating insulin level (J:145998) at birth and 2 weeks of age, mice exhibit increased serum insulin levels compared to in wild-type mice however, mice treated with isoproterenol exhibit lowered serum levels of insulin endocrine/exocrine glands increased pancreatic beta cell mass (J:145998) beta-cell proliferation, mass and area are increased compared to in wild-type mice abnormal pancreatic beta cell physiology (J:145998) beta-cell proliferation is increased compared to in wild-type mice increased insulin secretion (J:145998) insulin content in the pancreata is increased compared to in wild-type mice growth/size decreased body weight (J:145998) at 2 weeks of age decreased body mass index (J:145998) at 2 weeks of age digestive/alimentary system increased pancreatic beta cell mass (J:145998) beta-cell proliferation, mass and area are increased compared to in wild-type mice abnormal pancreatic beta cell physiology (J:145998) beta-cell proliferation is increased compared to in wild-type mice increased insulin secretion (J:145998) insulin content in the pancreata is increased compared to in wild-type mice
Genotype	Allelic Composition	Genetic Background
tg2	Tg(AZIP/F)1Vsn/0	involves: FVB/N
lethality/postnatal postnatal lethality (J:50807) normal numbers of transgenic pups are born however by weaning the percentage of transgenic pups is decreased to 30% (from 50%) almost no pups from litters produced by hemizygous females survive until weaning life span/aging increased sensitivity to xenobiotic induced morbidity/mortality (J:50807) transgenic mice are more sensitive to death after anesthesia than wild-type mice premature death (J:50807) survival after weaning is reduced adipose tissue decreased brown adipose tissue amount (J:50807) transgenic mice have decreased brown fat at birth which is primarily inactive and resembles white adipose tissue decreased white adipose tissue amount (J:50807) transgenic mice have essentially no white fat as a result of a failure to generate white adipose tissue cells behavior/neurological polydipsia (J:50807) transgenic mice drink 4 times more than wild-type mice digestive/alimentary system pancreatic islet hyperplasia (J:50807) the islet cells are hyperplastic and hypertrophic with a large increase in the number of beta cells endocrine/exocrine glands pancreatic islet hyperplasia (J:50807) the islet cells are hyperplastic and hypertrophic with a large increase in the number of beta cells growth/size weight loss (J:50807) when fasted adult transgenic mice lose weight faster than non-transgenic mice increased body weight (J:50807) transgenic mice are heavier than wild-type mice at 8-11 weeks of age as a result of an increase in the weights of multiple organs including the liver, heart, kidneys, and spleen transgenic mice have increased abdominal girth compared to wild-type mice postnatal growth retardation (J:50807) transgenic mice grow slower than wild-type mice before weaning, weighing 50% and 80% of wild-type weight at 1 and 3 weeks of age, respectively homeostasis/metabolism decreased circulating leptin level (J:50807) free active leptin levels are about 5% of wild-type mice abnormal glucose homeostasis (J:50807) hyperglycemia (J:50807) serum glucose is increased about 3-fold compared to wild-type mice elevated serum glucose is first detected 3 weeks after birth and reaches diabetic levels by 4 weeks when fasted serum glucose levels drop to a much greater extent than in non-transgenic mice increased circulating insulin level (J:50807) serum insulin levels are increased 58- and 442-fold in male and female transgenic mice insulin levels are already elevated 30-fold by 1 week after birth when fasted serum insulin levels drop to a much greater extent than in non-transgenic mice abnormal lipid homeostasis (J:50807) increased circulating free fatty acid level (J:50807) circulating free fatty acid are increased 1.5- to 2.5 fold compared to wild-type mice however no signs of ketosis are detected when fasted circulating free fatty acid levels drop rather than rise as in wild-type mice increased triglyceride level (J:50807) the livers of transgenic mice contain 6.8-fold higher triglyceride levels compared to wild-type mice increased circulating triglyceride level (J:50807) serum triglyceride levels are elevated 3- to 5-fold increased sensitivity to xenobiotic induced morbidity/mortality (J:50807) transgenic mice are more sensitive to death after anesthesia than wild-type mice liver/biliary system increased liver weight (J:50807) liver weight is increased 2.1-fold accounting for less than 50% of the total body weight increase in transgenic mice hepatic steatosis (J:50807) the liver is pale with lipid accumulation in a zone 3/centrilobular pattern renal/urinary system polyuria (J:50807) transgenic mice have a significantly higher urine output than normal reproductive system reduced female fertility (J:50807) females have reduced fertility and litter size with almost no pups surviving until weaning reduced male fertility (J:50807) male fertility is decreased but litters that are produced are of normal size respiratory system abnormal lung morphology (J:50807) lipid loaded phagocytic cells are seen in the lungs of some transgenic mice skin/coat/nails rough hair (J:50807)
Genotype	Allelic Composition	Genetic Background
tg3	Bglap1/Bglap2^tm1Kry/Bglap1/Bglap2^tm1Kry Tg(AZIP/F)1Vsn/0	involves: 129S7/SvEvBrd * FVB/N
homeostasis/metabolism increased circulating insulin level (J:145998) mice exhibit elevated serum insulin levels compared to in wild-type mice that are half as much as in Tg(AZIP/F)1Vsn mice
Genotype	Allelic Composition	Genetic Background
tg4	Bglap1/Bglap2^tm1Kry/Bglap1/Bglap2^tm1Kry Tg(AZIP/F)1Vsn/0	involves: 129S7/SvEvBrd * FVB/N
homeostasis/metabolism increased circulating insulin level (J:145998) mice exhibit elevated serum insulin levels compared to in wild-type mice that are half as much as in Tg(AZIP/F)1Vsn mice

Notes

The A-ZIP/F-1 phenotype suggests a mouse model for the human disease lipoatrophic diabetes (Seip-Berardinelli syndrome).

References

Original:	J:50807 Moitra J et al., "Life without white fat: a transgenic mouse." Genes Dev 1998 Oct 15;12(20):3168-81
All:	24 reference(s)

Contributing Projects: Mouse Genome Database (MGD), Gene Expression Database (GXD), Mouse Tumor Biology (MTB), Gene Ontology (GO), MouseCyc
Citing These Resources Funding Information Warranty Disclaimer & Copyright Notice Send questions and comments to User Support.	last database update 11/20/2009 MGI_4.31 Web browser compatibility