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Strain Name:

FVB-Tg(AZIP/F)1Vsn/J

Stock Number:

004100

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Genes & Alleles   Fabp4;   A-ZIP/F;   Tg(AZIP/F)1Vsn;

Product Information

Strain Details

Type JAX® GEMM® Strain - Coisogenic
Additional information on JAX® GEMM® Strains.
Type JAX® GEMM® Strain - Mutant Strain
Type JAX® GEMM® Strain - Transgenic
Specieslaboratory mouse
Donating Investigator Charles Vinson,   NCI, NIH

Strain Description
Mice expressing the A-ZIP/F gene under the control of 7.6kB of the adipocyte specific Fabp4 promoter have virtually no white adipose tissue and a reduced amount of brown adipose tissue. Brown adipose is found in lesser amounts as the animal ages. These mutant mice are very sensitive to cold temperature. Hemizygotes suffer from poor fecundity; the donating investigator indicates that not all males breed and pregnant females lactate inadequately. At birth, mice appear normal, losing weight in the first post-natal week but reach or exceed wildtype weight by 8-11 weeks. Adult mice display polyphagia and polydypsia, eating and drinking several times more than wildtype mice. Urine output is greatly increased. Transgenic mice have a characteristic rough-appearing coat and increased abdominal girth attributed to enlarged viscera. Most notably affected is the liver. Histological examination of liver tissue reveals numerous lipid droplets. Pancreatic islets are hypertrophic and hyperplastic with large increases in beta cell numbers observed. Adult mice exhibit elevated levels of glucose, insulin, free fatty acids and triglycerides. Increased insulin levels are observed as early as 5 weeks of age. Circulating levels of free, active leptin are greatly diminished. This strain represents a model useful for studying lipoatrophicdiabetes and the contribution of fat tissue to metabolic equilibrium.

Strain Development
A transgenic construct containing the A-ZIP/F gene under the direction of a fatty acid binding protein 4, adipocyte promoter/enhancer was injected into male pronuclei of FVB/N mice. Founder animals were obtained and mated with FVB/N mice.

Mammalian Phenotype Terms assigned by genotype

Tg(AZIP/F)1Vsn/0

        involves: FVB/N
  • lethality-postnatal
  • postnatal lethality (MGI Ref ID 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-post-weaning/aging
  • abnormal induced morbidity/mortality (MGI Ref ID J:50807)
    • transgenic mice are more sensitive to death after anesthesia than wild-type mice
  • premature death (MGI Ref ID J:50807)
    • survival after weaning is reduced
  • adipose tissue phenotype
  • decreased brown adipose tissue amount (MGI Ref ID J:50807)
    • transgenic mice have decreased brown fat at birth which is primarily inactive and resembles white adipose tissue
  • decreased white adipose tissue amount (MGI Ref ID J:50807)
    • transgenic mice have essentially no white fat as a result of a failure to generate white adipose tissue cells
  • behavior/neurological phenotype
  • polydipsia (MGI Ref ID J:50807)
    • transgenic mice drink 4 times more than wild type mice
  • digestive/alimentary phenotype
  • islet cell hyperplasia (MGI Ref ID J:50807)
    • the islet cells are hyperplastic and hypertrophic with a large increase in the number of beta cells
  • endocrine/exocrine gland phenotype
  • islet cell hyperplasia (MGI Ref ID J:50807)
    • the islet cells are hyperplastic and hypertrophic with a large increase in the number of beta cells
  • growth/size phenotype
  • increased body weight (MGI Ref ID 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 (MGI Ref ID 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
  • weight loss (MGI Ref ID J:50807)
    • when fasted adult transgenic mice lose weight faster than non-transgenic mice
  • homeostasis/metabolism phenotype
  • abnormal glucose homeostasis (MGI Ref ID J:50807)
    • hyperglycemia (MGI Ref ID 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 (MGI Ref ID 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 (MGI Ref ID J:50807)
    • increased circulating free fatty acid level (MGI Ref ID 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 (MGI Ref ID J:50807)
      • the livers of transgenic mice contain 6.8-fold higher triglyceride levels compared to wild-type mice
      • increased circulating triglyceride level (MGI Ref ID J:50807)
        • serum triglyceride levels are elevated 3- to 5-fold
  • decreased circulating leptin level (MGI Ref ID J:50807)
    • free active leptin levels are about 5% of wild type mice
  • liver/biliary system phenotype
  • hepatic steatosis (MGI Ref ID J:50807)
    • the liver is pale with lipid accumulation in a zone 3/centrilobular pattern
  • increased liver weight (MGI Ref ID J:50807)
    • liver weight is increased 2.1-fold accounting for less than 50% of the total body weight increase in transgenic mice
  • renal/urinary system phenotype
  • polyuria (MGI Ref ID J:50807)
    • transgenic mice have a significantly higher urine output than normal
  • reproductive system phenotype
  • reduced female fertility (MGI Ref ID J:50807)
    • females have reduced fertility and litter size with almost no pups surviving until weaning
  • reduced male fertility (MGI Ref ID J:50807)
    • male fertility is decreased but litters that are produced are of normal size
  • respiratory system phenotype
  • abnormal lung morphology (MGI Ref ID J:50807)
    • lipid loaded phagocytic cells are seen in the lungs of some transgenic mice
  • skin/coat/nails phenotype
  • rough hair (MGI Ref ID J:50807)

Gene & Allele Details

Allele Symbol Tg(AZIP/F)1Vsn
Allele Name transgene insertion 1, Charles Vincent
Common Name(s) A-ZIP/F-1;
Mutation Made By Charles Vinson,   NCI, NIH
Strain of OriginFVB/N
Expressed Gene A-ZIP/F, flag epitope/leucine zipper, artificial
Promoter Fabp4, fatty acid binding protein 4, adipocyte, mouse, laboratory
General Note The A-ZIP/F-1 phenotype suggests a mouse model for the human disease lipoatrophic diabetes (Seip-Berardinelli syndrome).
Molecular Note 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. [MGI Ref ID J:50807]

Control Information

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   Noncarrier
 
  Considerations for Choosing Controls

Genotyping Protocols

Tg(AZIP/F)1Vsn

Colony Maintenance

Breeding & HusbandryThese mice originated on an FVB/N background and have been maintained as hemizygotes by breeding to FVB mice. Hemizygotes suffer from poor fecundity; the donating investigator indicates that not all males breed and pregnant females lactate inadequately. Use of nestlets recommended due to cold sensitivity and extra absorbent bedding due to excessive urination.
Diet Information LabDiet® 5K52/5K67

Related Strains

Strains carrying other alleles of Fabp4
005069   B6.Cg-Tg(Fabp4-cre)1Rev/J
003393   B6;SJL-Tg(aP2-SREBF1c)9884Reh/J
View Strains carrying other alleles of Fabp4     (2 strains)

Research Applications

This mouse can be used to support research in many areas including:

Diabetes and Obesity Research
Hyperglycemia
Hyperinsulinemia
Type 2 Diabetes (NIDDM)

Metabolism Research
Lipid Metabolism

References

Selected Reference(s)

Moitra J; Mason MM; Olive M; Krylov D; Gavrilova O; Marcus-Samuels B; Feigenbaum L; Lee E; Aoyama T; Eckhaus M; Reitman ML; Vinson C. 1998. Life without white fat: a transgenic mouse. Genes Dev 12(20):3168-81. [PubMed: 9784492]  [MGI Ref ID J:50807]

Additional References

Price and Supply Information

Strain Name: FVB-Tg(AZIP/F)1Vsn/J
Stock Number: 004100

Price Details

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Supply Details

Standard SupplyRepository-Cryopreserved. Must Be Recovered. Please refer to pricing and supply notes for further information.
Supply Notes Cryorecovery - Standard.
The recovery process begins when a signed agreement form is returned to the Customer Service Department after order placement. Although results vary by strain, at least two males and two females (two pairs) will be provided, typically within 15 weeks of our receipt of the signed agreement form. If the first recovery attempt is unsuccessful or only one pair is recovered, a second recovery will be done, extending the delivery time to approximately 25 weeks. At least one member of each pair will be of known genotype and will carry the mutation if it is a mutant strain. Please note that pairs may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation of the strain. Mating schemes are sometimes modified for successful cryopreservation. Price represents a repository maintenance fee, which includes the cost of recovery of the strain from the cryopreservation resource and the periodic replacement of the frozen embryos used for recovery.

Cryorecovery to establish a Dedicated Supply for greater quantities of mice.
One to two pairs will be recovered to establish a Dedicated Supply of mice. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services: Tel: 1-800-422-6423 or 1-207-288-5845; Email: jaxservices@jax.org.
This strain is included in the Induced Mutant Resource Colony collection.
Genomic DNA is available for this strain from the Mouse DNA Resource.

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The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project.
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