These mice carry a spontaneous mutation at the Tub locus characterized by maturity-onset obesity.
Read More +Genetic Background | Generation |
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000928 CAST/EiJ |
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Allele Type | Gene Symbol | Gene Name |
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Spontaneous | Tub | tubby bipartite transcription factor |
Mice homozygous for the tubby spontaneous mutation experience maturity-onset obesity. Homozygous mutant mice are recognizable by increased body weight at 3 to 4 months in males and at 4 to 6 months in females. Both sexes are fertile. The increased weight is composed of excess adipose tissue. Blood glucose is normal, but plasma insulin is increased prior to obvious signs of obesity and may rise to 20 times normal by 6 months on the C57BL/6 background. Despite elevated plasma total cholesterol, triglycerides, and high-density lipoprotein cholesterol, homozygous mutant mice do not exhibit atherosclerotic fatty streak blood vessel lesions. Tubby mutant mice also exhibit retinal degeneration, initially believed due to the presence of another mutation which was called rd5, but since demonstrated to be a pleiotropic effect of the Tubtub mutation (Ohlemiller et al., 1997); the retinal phenotype is moderated by a QTL on Chromosome 11 (Ikeda et al., 2002). Tubby homozygotes additionally exhibit progressive hearing loss. The hearing loss is due to apoptotic degeneration of the organ of Corti and loss of afferent neurons. Quantitative trait locus (QTL) analysis identified a region on Chromosome 2 (designated modifier of tubby hearing 1, moth1) whose wild-type allele protects tubby mice from hearing loss (Ikeda et al., 1999); the gene has been identified as Mtap1a, encoding a microtubule-associated protein (Ikeda et al., 2002). A locus suggestively associated with protection from retinal degeneration maps to the same region of Chromosome 2 (Ikeda et al., 2002). Mice homozygous for a targeted null mutation in the tubby gene (not currently available from The Jackson Laboratory) exhibit a phenotype identical to that conferred by the spontaneous tubby mutation (Stubdal, et al., 2000).
Homozygous mice on the CAST background exhibit a phenotype similar to the published C57BL/6 background, however, they are smaller in size (personal communication).
Allele Name | tubby |
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Allele Type | Spontaneous |
Allele Synonym(s) | rd5; tub |
Gene Symbol and Name | Tub, tubby bipartite transcription factor |
Gene Synonym(s) | |
Strain of Origin | C57BL/6J |
Chromosome | 7 |
General Note | The phenotype associated with retinal degeneration in the tubby stock was referred to as a separate locus, rd5. rd5 was identified in the tubby stock but absent from the parental C57BL/6J stock. Based on the tight linkage of the two phenotypes and the molecular defect underlying the tub mutation, it seemed likely that tub and rd5 were the same gene. This was further supported by a knockout of the tub gene that recapitulated the retinal degeneration phenotype. |
Molecular Note | A G-to-T mutation of the first nucleotide of intron 11 eliminates exon 11 splice donor site G-GT by changing it to G-TT, leading to mis-splicing in the form of retention of intron 11. |
When using the Tubby mouse strain in a publication, please cite the originating article(s) and include JAX stock #003711 in your Materials and Methods section.
Facility Barrier Level Descriptions
Service/Product | Description | Price |
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Homozygous, Heterozygous or Wild-type for Tub<tub>, 1 pair minimum |
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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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