This strain may be segregating for the Oca2p and s alleles of Hbb.
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. 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).
The Tubtub mutation arose spontaneously in 1977 in The Jackson Laboratory Animal Resources colony of C57BL/6J which was then at F125. After initial maintenance on the C57BL/6J background, a C57BL/6J-Tubtub homozygous male was bred with a female congenic B6.AU-Hbbp and the Hbbp +/Hbbs Tubtub offspring were sibling mated. The colony was maintained by breeding siblings Hbbp +/Hbbs Tubtub x Hbbp +/Hbbs Tubtub or vice versa for many years and in 2002 reached F87. In 2004 isozyme testing for Hbb alleles was replace with PCR testing for the Tubtub allele and the colony reached F90. (Coleman et al., 1978; Coleman and Eicher, 1990.)
|Allele Synonym(s)||Tubtub; tubby|
|Gene Symbol and Name||Tub, tubby bipartite transcription factor|
|Gene Synonym(s)||rd5; retinal degeneration 5; rd5; tubby; RDOB; tub; tub|
|Strain of Origin||C57BL/6J|
|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 donor splice site in the 3' region of the gene is abolished by a G to T transversion resulting in a larger transcript containing the unspliced intron.|
This strain was maintained for many years by breeding Hbbp +/Hbbs Tubtub + x Hbbs Tubtub/Hbbs Tubtub or vice versa. Hbb and Tub are approximately 1.5 cM apart on Chromosome 7. Tubby heterozygotes were distinguished from homozygotes by typing for the Hbb allele. This was done by cellulose acetate gel analysis of cystamine treated red blood cell lysates as described by Whitney, 1978. The Hbbs allele yields a single fast migrating band of hemoglobin while the Hbbp allele yields a slow migrating band and a second smaller, trailing band that may actually have cathodal migration on cellulose acetate (but not in starch or acrylamide gels). The mice carrying only the Hbbs allele were presumed homozygous for the Tubtub mutation by linkage; those with both the Hbbs and Hbbp alleles were presumed heterozygous for Tubtub by linkage. In 2004 genotyping of the Tubtub allele by PCR became the standard method for colony maintenance. Recombination can be expected to eventually remove the Hbbp allele from this strain. Heterozygous females are better mothers than homozygous females.
When using the tubby mouse strain in a publication, please cite the originating article(s) and include JAX stock #000562 in your Materials and Methods section.
|Heterozygous or Wild-type for Tub<tub>|
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