D2.BKS(D)-Lepr^db/J

Stock number: 012666
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

Description

Mutant mice on this background will be useful in studies to establish the nature of diabesity modifier genes in the DBA/2 genome as well as the development of diabetic complications, notably diabetic nephropathy and glaucoma.

Detailed description

Recessive mutations in the leptin receptor produce massive obesity regardless of the strain background on which they are studied. However, development of obesity-induced and insulin resistant diabetes ("diabesity") is strongly influenced by inbred strain background modifier genes and by sex. A comparison of this mutation on multiple inbred backgrounds showed that the congenic transfer of the mutation from the diabesity-susceptible C57BLKS/J background onto the DBA/2J background produced an even more severe diabesity syndrome (Leiter et al., 1981). This is noteworthy because C57BLKS/J is thought to differ from the diabesity-resistant C57BL/6J strain by the presence of DBA/2 genetic contamination in a B6-like genome (Naggert et al., 1995). Unfortunately, this D2.BKS-Lepr^db stock was not maintained. Because diabetic DBA/2J males have been shown to be more susceptible to development of diabetic nephropathy (Gurley et al., 2010), speed congenic methodology was used to regenerate this mutant stock. Mutant mice on this background will be useful in studies to establish the nature of diabesity modifier genes in the DBA/2 genome (Davis et al., 2012) as well as the development of diabetic complications, notably diabetic nephropathy and glaucoma.

Heterozygous mice are either grey or dilute in appearance .

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 (BKS). Using marker assisted technology, the Type 1 Diabetes Resource and Genetic Resource Sciences established the "D2-db" congenic strain by introducing the Lepr^db allele from the BKS.Cg-m +/+ Lepr^db/J repulsion stock (see Stock No. 000642) onto the DBA/2J (see Stock No. 000671) background. In 2012, "D2-db" mice generated using speed congenic technology were rederived into the Repository and are at the 6th backcross generation.

Allele

Symbol: Lepr^db
Name: diabetes
MGI accession ID: MGI:1856009
Generation method: Spontaneous
Synonyms: db; db/db; Lep^db; Lepr-; Lepr^db-1J; leprdb
Marker symbol: Lepr
Marker name: leptin receptor
Marker synonyms: CD295; Fa; LEP-R; Leprb; LEPRD; LEPROT; leptin receptor gene-related protein; Modb1; obese-like; obl; Obr; OB-R; OB-RGRP
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