These mice carry a spontaneous mutation at the Lepr locus on a CBA/J background and are characterized by exocrine pancreatic necrosis and kidney lesions in aging mice. Homozygous males progressively develop severe hyperglycemia. The strain carries the misty mutation (Dock7m) to aid in early identification of homozygotes.Read More +
Leprdb/Leprdb mice on the CBA strain background are characterized by exocrine pancreatic necrosis and kidney lesions in aging mice. In contrast to the obesity observed in other strain backgrounds, five month old homozygous males exhibit weight loss in comparison to controls. Homozygous males develop severe hyperglycemia exhibiting blood sugar levels of +/-475 mg/dl by three months of age and increasing to +/- 517 mg/dl by five months. Five month old homozygous males do not exhibit hyperinsulinemia, however homozygous females reach levels of +/-540 uU/ml. Homozygous males do not survive beyond six months (Leiter EH et al, 1981).
Because of the sterility of Leprdb homozygotes, misty has been incorporated into stocks for maintenance of the diabetes mutation. The repulsion double heterozygote (Leprdb +/+ Dock7m) facilitates identification of heterozygotes for breeding, while the coupling double heterozygote, (Leprdb Dock7m/+ +) allows identification of homozygotes before the phenotype becomes severe.
The recessive misty mutation causes a mild dilution of coat color and on certain backgrounds a white tail tip often accompanied by a belly spot. Melanocytes from Dock7m/Dock7m mice have a highly dendritic shape, show deficient proliferation in culture and have much more melanin content. Fewer melanoblasts are found in primary cultures from Dock7m/Dock7m mice than from wildtype controls. Between two and five weeks of age, Dock7m/Dock7m mice are smaller than controls. At 35 days of age they are shorter, weigh 15% less on average, and have less inguinal adipose mass than controls. Misty homozygotes completely lack brown fat. Although platelet count, seratonin content and ATP content are normal, there is increased bleed time and reduced platelet AD levels in Dock7m/Dock7m homozygotes. (Woolley, 1941 and 1945; Truett et al, 1998; Sviderskaya et al, 1998.)
The spontaneous autosomal recessive mutation diabetes,db was discovered at The Jackson Laboratory, Bar Harbor, ME in 1966 on the inbred strain C57BLKS/J. Formerly known as db , after cloning it became Leprdb. The background strain, CBA/JLsLt is a closed subline held by Dr. Ed Leiter at The Jackson Laboratory derived from CBA/JLs. CBA/JLs, held by Dr. Ed Les, was separated from CBA/J in 1978 (Leiter EH, 1981). This congenic was backcrossed seven times by cross-intercross matings. In 1995, wild-type CBA/J females were bred with heterozygous males (N7F42) to generate embryos for cryopreservation in 1988.
|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.|
|Gene Symbol and Name||Dock7, dedicator of cytokinesis 7|
|Strain of Origin||DBA/J|
|Molecular Note||Crosses between mice homozygous for misty and for moonlight, which mapped to overlapping critical regions on Chr 4, demonstrated failure of the two mutations to complement one another. Once moonlight had been identified as a mutation of Dock7 (Dock7mnlt), sequence analysis of this gene from misty mice revealed a retrotransposon LTR insertion following nucleotide 2045 (numbering from the A of the transcription initiation codon) that interrupts exon 18 and shifts the reading frame after codon 682 so that ten incorrect amino acids are incorporated into the protein before its premature termination.|
When using the CBA-diabetes mouse strain in a publication, please cite the originating article(s) and include JAX stock #000707 in your Materials and Methods section.