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.
Streamson Chua, Albert Einstein College of Medicine
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.
The spontaneous autosomal recessive diabetes (Leprdb) mutation was discovered at The Jackson Laboratory, Bar Harbor, Maine USA in 1966 on the inbred strain C57BLKS/J. Because Leprdb 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 Leprdb allele from the BKS.Cg-m +/+ Leprdb/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 Synonym(s)||db; db/db; Lepdb; Lepr-; Leprdb-1J; leprdb|
|Gene Symbol and Name||Lepr, leptin receptor|
|Strain of Origin||C57BLKS/J|
|General Note|| |
Phenotypic Similarity to Human Syndrome: Gestational Diabetes J:219658
|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.|
When maintaining a live colony, heterozygous mice are bred together. The donating investigator maintains these mice on a gamma-irradiated diet (PicoLab 5058, PMI Nutritional International, Richmond, Ind., USA) containing a minimum of 9% fat content by weight. This diet was chosen to mimic the diet provided by The Jackson Laboratories to their FVB/NJ inbred strain.
When using the FVB-diabetes mouse strain in a publication, please cite the originating article(s) and include JAX stock #006654 in your Materials and Methods section.
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