Homozygous Cyb5r4tm1Hfb mice exhibit clinical diabetes and reduction in the number of islets in the pancreas.
H. F. Bunn, Brigham and Womens Hospital
Genetic Background | Generation |
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|
Allele Type | Gene Symbol | Gene Name |
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Targeted (Null/Knockout) | Cyb5r4 | cytochrome b5 reductase 4 |
Mice heterozygous for the targeted mutation are viable and fertile, glucose tolerant, have normal blood sugar levels, serum lipid profiles and white adipose tissue mass.
No protein from the targeted gene was detected by Western Blot analysis of mice homozygous for the allele. Homozygous mice consume more food, have decreased adipose tissue mass and are hyperlipidemic compared to wildtype controls post-weaning. At 4 weeks of age glucose levels are normal but insulin levels are 40% of wildtype controls. At 7 weeks of age clinical diabetes is present in both male and female of homozygous mice. Histological evaluation of pancreas from 21 week old homozygote animals revealed a significant reduction in the number of islets and decreased cytoplasmic to nuclear ratio in the islet cells and there was no insulitis nor phagocytosis of necrotic beta cell fragments. While there is a progressive loss of beta cells in aging homozygous mice, there is no loss of alpha, delta or PP cells. Electron microscopy reveals degranulated beta cells and hypertrophic and hyperplastic mitochodria.
This strain is useful in islet transplantation research, stem cell research and as a tool for studying the role of oxidative stress in diabetes.
A construct containing a hygromycin expression cassette replaces a region extending from the 3' end of exon 3 to the 5' end of intron 4 of Cyb5r4 (cloned from a 129/Sv mouse), deleting exon 4 the heme binding domain crucial to enzyme stability and biochemical properties, was transfected into 129S4/SvJae embryonic stem cells (ES cells). These ES cells were injected into C57BL/6 blastocysts. Chimeric founders were mated to C57BL/6 and subsequently intercrossed to generate homozygotes. In 2005, the Type 1 Diabetes Resource received heterozygous B6.129S4-Cyb5r4tm1Hfb/HfbJ at generation N9.
Allele Name | targeted mutation 1, H Franklin Bunn |
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Allele Type | Targeted (Null/Knockout) |
Allele Synonym(s) | Ncb5or- |
Gene Symbol and Name | Cyb5r4, cytochrome b5 reductase 4 |
Gene Synonym(s) | |
Strain of Origin | 129S4/SvJae |
Chromosome | 9 |
Molecular Note | Exon 4, which contains sequence encoding the heme-binding domain, was replaced with a PGK-hygromycin gene. Mutant mice did not express full length mRNA or protein, as shown by Northern blot and Western blot, respectively. |
Mutations Made By | H. Bunn, Brigham and Womens Hospital |
When maintaining a live colony, heterozygous mice may be bred to wildtype mice from the colony. Due to early diabetes onset, the colony is not maintained by homozygote matings.
When using the B6.Ncb5or,sup>null mouse strain in a publication, please cite the originating article(s) and include JAX stock #005517 in your Materials and Methods section.
Facility Barrier Level Descriptions
Service/Product | Description | Price |
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Heterozygous or Wild-type for Cyb5r4<tm1Hfb> |
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The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project. We do not guarantee breeding performance and therefore suggest that investigators order more than one breeding pair to avoid delays in their research.
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