FVB.BKS(D)-Lepr^db/ChuaJ

Stock number: 006654
Product name: FVB-diabetes
Strain synonyms: FVB.C57BLKS-Lepr^db, FVB-Lepr^db, FVB-db
Research areas: Diabetes and Obesity Research, Endocrine Deficiency Research, Immunology, Inflammation and Autoimmunity Research, Internal/Organ Research, Metabolism Research, Mouse/Human Gene Homologs, Reproductive Biology Research, Research Tools

Description

The congenic "FVB-db" strain presents an obesity/diabetes phenotype different from db on other genetic backgrounds. These mice may be useful for diabetes research, including the dissection of genetic control of beta-cell responses to hyperglycemia and insulin resistance/sensitivity.

Detailed description

The congenic "FVB-db" strain differs from that previously published on other genetic backgrounds in that it presents a marked obesity/diabetes phenotype intermediate between the severe uncompensated hyperglycemia observed in C57BLKS/J and DBA2/J backgrounds and the mild, compensated syndrome reported on the C57BL/6J and 129/J backgrounds. The literature reports that obese FVB-db mice of both sexes show long-term hyperglycemia primarily due to severe insulin resistance. The hyperglycemia in the fed state persists despite continued extreme hyperinsulinemia correlated with a marked pancreatic cell hypertrophy and hyperplasia. These phenotypes have been replicated in the stock at The Jackson Laboratory. However, the diabetic nephropathy (glomerulosclerosis) reported in the literature was not evident in the stock imported to JAX at the age evaluated (24 weeks).

As the phenotype varies by genetic background, these mutant mice, along with db mutants on other genetic backgrounds (see Stock No. 000642, 000697, 000699, 000700, and 000707), may be useful for diabetes research, including the dissection of genetic control of beta-cell responses to hyperglycemia and insulin resistance/sensitivity.

Development

The spontaneous autosomal recessive diabetes (Lepr^db) mutation was discovered at The Jackson Laboratory, Bar Harbor, Maine USA in 1966 on the inbred strain C57BLKS/J. Because Lepr^db homozygotes are sterile, the misty (m) mutation from DBA/J was incorporated into stocks for maintenance of the diabetes mutation. This "FVB-db" congenic strain was generated in the laboratory of Dr. Streamson Chua, Jr. (Albert Einstein College) by introducing the Lepr^db allele from the BKS.Cg-m +/+ Lepr^db/J repulsion stock (see Stock No. 000642) onto the FVB/NJ background. Following 10 generations of backcrossing to FVB/NJ, this strain was maintained by breeding heterozygous mice together for at least 17 generations prior to arrival at The Jackson Laboratory. The donating investigator indicates that the misty mutation was not retained during the backcrossing.

Allele

Symbol: Lepr^db
Name: diabetes
MGI accession ID: MGI:1856009
Generation method: Spontaneous
Marker symbol: Lepr
Marker name: leptin receptor
Chromosome: 4
Strain of origin: C57BLKS/J
Molecular note: An intronic G-to-T transversion in this allele created a donor splice site that causes abnormal splicing and the inclusion of 106 nt of intronic sequence in the transcript, leading to premature termination of the long cellular domain of the Ob-Rb splice form and loss of its signal transducing function.
General note:

Phenotypic Similarity to Human Syndrome: Gestational Diabetes J:219658