Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Using 180 F2 progeny of a C57BL6/J >< CAST/Ei tub/+F1 intersubspecific intercross, a map of 28 molecular markers (including eight genes) on chromosome 7 surrounding the tub locus was generated. Using 33 obese F2 progeny, tub was localized approximately 50-52 cM distal to the centromere on mouse chromosome 7 in the interval defined proximally by hemoglobin beta (Hbb), D7Mit38, D7Mit2l7, D7Mit37, D7Mit96, and D7Mit33 and distally by D7Mit98. Using 39 obese F2 progeny from a similar intersubspecific intercross, a telomeric boundary of the interval defining tub was defined by D7Mit53; the order centromere-Hbb/tub-D7Mit53/ D7Mit328/D7Mit220-parathyroid hormone (Pth)-calcitonin (Calc)-zona pellucida 2 (2p2) was established. By combining the data from the two crosses, the most likely gene order on mouse chromosome 7 is centromere-Hbb-tub-Pth-Calc, thus making it likely that the human homolog of tub resides on 17p15, where the gene order HBB-PTH-CALC is conserved. Assignment of the human tubby homolog to 17p15 allows selection and development of polymorphic molecular markers that can be used to examine segregation of a human homolog of tubby in pedigrees segregating for obesity. The gene sulfonylurea receptor was eliminated as a candidate gene for tubby on the basis of its map position, approximately 3.1 +/- 3.1 cM centromeric of tyrosinase and approximately 14.9 +/- 4.8 cM centromeric of Hbb.
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PMID:Molecular mapping of the tubby (tub) mutation on mouse chromosome 7. 883 47

Mice homozygous for a defect of the tub (rd5) gene exhibit cochlear and retinal degeneration combined with obesity, and resemble certain human autosomal recessive sensory deficit syndromes. To establish the progressive nature of sensory cell loss associated with the tub gene, and to differentiate tub-related losses from those associated with the C57 background on which tub arose, we evaluated cochleas and retinas from tub/tub, tub/+, and +/+ mice, aged 2 weeks to 1 year by light and electron microscopy. Cochleas from mice of all three genotypes show progressive inner (IHC) and outer hair cell (OHC) loss. Relative to tub/+ and +/+ animals, however, tub homozygotes show accelerated OHC loss, affecting the extreme cochlear base (hook region) by 1 month, and the apex by 6 months. IHC loss in tub/tub animals is accelerated in the basal half of the cochlea, affecting the hook region by 6 months. Spiral ganglion cell losses were observed only in tub/tub mice, and only in the cochlear base. Retinas of tub/tub mice are abnormal at maturity, exhibiting shortened photoreceptor outer segments by 2 weeks, and progressive photoreceptor loss thereafter. Because the tub mutation causes degeneration of sensory cells in the ear and eye but has no other neurological effects, tubby mice hold unique promise for the study of human syndromic sensory loss.
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PMID:Progression of cochlear and retinal degeneration in the tubby (rd5) mouse. 939 Aug 31

Some genetic syndromes causing loss of hearing and vision, such as some forms of Usher's syndrome, also cause reduced sperm cell motility, bronchiectasis, and other pathologies involving cilia- and flagella-bearing cells. In some Usher's patients, ultrastructural defects of axonemes within photoreceptor ciliary bridges, nasal cilia, and sperm cell flagella have been found, indicating a primary defect of axonemal conformation. Mice homozygous for the tub (rd5) mutation exhibit progressive retinal degeneration, sensorineural hearing loss, reduced fertility, and obesity, and presently represent the only animal model with neuroepithelial degeneration of both cochlea and retina without other neurological abnormalities. They provide a good phenotypic match to human genetic sensory syndromes, particularly human sensory/obesity syndromes, such as Alstrom's and Bardet/Biedl, although no human candidate genes have been identified. Because of their unique phenotype, tubby mice are an appropriate model in which to look for a primary axonemal defect. We studied the axonemal ultrastructure of photoreceptors and sperm cells and performed functional testing of sperm in tub/tub mice before and after the onset of obesity. Approximately 15% of photoreceptor axonemes appeared abnormal in tub/tub animals, compared to 0% in controls. Both tub homozygotes and controls exhibited approximately 10% abnormal sperm cell axonemes, and no differences in sperm cell motile function were found at any age. The modest occurrence of axonemal defects in photoreceptors of tub/tub animals is likely to be a secondary effect of retinal degeneration. We conclude that the tubby phenotype is not associated with a generalized defect of cilia- and flagella-bearing cells and that the tub mutation does not primarily affect axonemal structure.
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PMID:The murine tub (rd5) mutation is not associated with a primary axonemal defect. 947 5