These mice carry a spontaneous mutation at the Lepr locus on a C57BLKS/J background and are characterized by obesity, elevation of blood sugar, depletion of insulin-producing beta-cells of the pancreatic islets, and early death. The strain carries the misty mutation (Dock7m) to aid in early identification of homozygotes.Read More +
Mice homozygous for the diabetes spontaneous mutation (Leprdb) become identifiably obese around three to four weeks of age. Elevations of plasma insulin begin at 10 to 14 days and of blood sugar at four to eight weeks. Homozygous mutant mice are polyphagic, polydipsic, and polyuric. The course of the disease is markedly influenced by genetic background. A number of features are observed on the C57BLKS background, including an uncontrolled rise in blood sugar, severe depletion of the insulin-producing beta-cells of the pancreatic islets, and death by 10 months of age. Exogenous insulin fails to control blood glucose levels and gluconeogenic enzyme activity increases. Peripheral neuropathy and myocardial disease are seen in C57BLKS Leprdb homozygotes. Wound healing is delayed and metabolic efficiency is increased. Although normal in body weight, blood glucose, and plasma insulin, heterozygotes (Leprdb/+) also have increased metabolic efficiency and can survive a prolonged fast longer than controls. Experiments involving destruction of the ventromedial nucleus of the hypothalamus suggest that Leprdb may cause a defect in the hypothalamus. Steroid sulfotransferase enzymes, aberrantly expressed in diabetic mice, interact with the Leprdb mutation as modifiers of gender differences in obesity-induced diabetes susceptibility. 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 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 wild-type 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 strain was cryopreserved in 1991 by mating Dock7m Leprdb/+ + males to C57BLKS/J females.
|Allele Synonym(s)||misty; Dock7m|
|Gene Symbol and Name||Dock7, dedicator of cytokinesis 7|
|Gene Synonym(s)||Gm430; ZIR2; RIKEN cDNA 3110056M06 gene; gene model 430, (NCBI); m; 3110056M06Rik; m; misty; 3110056M06Rik; mKIAA1771; LOC242555; EIEE23|
|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.|
|Allele Synonym(s)||Leprdb; diabetes|
|Gene Symbol and Name||Lepr, leptin receptor|
|Gene Synonym(s)||diabetes; OB-R; OB-RGRP; obese-like; obl; OBR; CD295; LEP-R; Leprb; LEPRD; LEPROT; obl; Modb1; leptin receptor gene-related protein; obese-like; db; Fa; Obr|
|Strain of Origin||C57BLKS/J|
|General Note|| |
Phenotypic Similarity to Human Syndrome: Gestational Diabetes J:219658
|Molecular Note||A G-to-T transversion in this allele created a donor splice site that causes abnormal splicing and a 106 nt insertion 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 using the BKS-diabetes mouse strain in a publication, please cite the originating article(s) and include JAX stock #000700 in your Materials and Methods section.
|Heterozygous for m, Heterozygous for Lepr<db>|
A molecular assay to genotype this strain is not available. We will fulfill your order by providing at least two untested males and two untested females (two pairs). The total number, sex, and genotypes will vary, although typically 8 or more mice are provided. Untested animals typically are available to ship between 10 and 14 weeks from the date of your order. If the first recovery attempt is unsuccessful, a second recovery will be done, extending the overall recovery time to approximately 25 weeks. Progeny testing may be required – If recovered animals do not display a phenotype, progeny testing will be required. This testing involves breeding the recovered animals and assessing the phenotype of the offspring in order to identify animals carrying the mutation of interest. Please note that identified 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. We cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.
Cryorecovery to establish a Dedicated Supply for greater quantities of mice. Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation.
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