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Gene Review

Tub  -  tubby candidate gene

Mus musculus

Synonyms: Rd5, Tubby protein, rd5, tub
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Disease relevance of Tub


High impact information on Tub


Chemical compound and disease context of Tub


Biological context of Tub

  • To test the hypothesis that mutations within other members of this gene family would lead to similar phenotypes as observed in tubby mice, and hence have similar functional properties, we have generated null mutants of the tubby-like protein ( Tulp ) 1 gene by homologous recombination [3].
  • Mice carrying different tulp1/tubby allele combinations were examined by histology, electroretinograms (ERGs), and immunofluorescence microscopy [10].
  • Here we show that tubby functions in signal transduction from heterotrimeric GTP-binding protein (G protein)-coupled receptors [11].
  • Tubby, an autosomal recessive mutation, mapping to mouse chromosome 7, was recently found to be the result of a splicing defect in a novel gene with unknown function [12].
  • We report a mouse model of type I Usher syndrome, rd5, whose linkage on mouse chromosome 7 to Hbb and tub has homology to human Usher I reported on human chromosome 11p15 [13].

Anatomical context of Tub


Associations of Tub with chemical compounds

  • Similarly, an age and body mass-dependent induction (about 30-fold) of neuropeptide Y (NPY) mRNA was observed in the dorsomedial (DMH) and ventromedial (VMH) hypothalamic nuclei of the tubby mice [16].
  • Compared with control mice, obese, diabetes, tubby, and lethal yellow mice had triglyceride levels that were elevated 1.5-fold to twofold, but fat mice had triglyceride levels similar to those of controls [17].
  • Natural killer (NK) cell activity is inhibited by the adenosine analogue tubercidin (Tub) and stimulated by the deoxyadenosine analogue 2-fluoro-1-beta-D-arabinofuranosyladenine 5'-monophosphate (F-ara-AMP) in the spleen lymphocytes from mice treated with the drugs in vivo (T. Priebe et al., Cancer Res., 48:4799, 1988) [18].
  • In concordance with this, tubby mice show higher excretion of ketone bodies and accumulation of glycogen in the liver [19].
  • Quantitation of liver mRNA levels shows that, during the transition from light to dark period, tubby mice fail to induce glucose-6-phosphate dehydrogenase (G6pdh), the rate-limiting enzyme in the pentose phosphate pathway that normally supplies NADPH for de novo fatty acid synthesis and glutathione reduction [19].

Other interactions of Tub

  • Localization of insulin-2 (Ins-2) and the obesity mutant tubby (tub) to distinct regions of mouse chromosome 7 [20].
  • The hearing modifier (Moth1) of tubby (Tub(tub)) mutant mice was shown to be a strain variant of the Mtap1a gene [21].
  • However, NPY mRNA in the ARC was decreased by approximately 30 to 40% in both juvenile and mature tubby mice [16].
  • In comparison with the wild-type controls, a significant reduction (20%) of pro-opiomelanocortin (POMC) mRNA expression was observed in the arcuate nucleus (ARC) of the mature, obese but not in the juvenile, non-obese tubby mice [16].
  • In addition, we show that Tub protein expression is not significantly altered in the ob, db, or melanocortin 4 receptor-deficient mouse model of obesity [22].

Analytical, diagnostic and therapeutic context of Tub


  1. Tubby proteins: the plot thickens. Carroll, K., Gomez, C., Shapiro, L. Nat. Rev. Mol. Cell Biol. (2004) [Pubmed]
  2. Microtubule-associated protein 1A is a modifier of tubby hearing (moth1). Ikeda, A., Zheng, Q.Y., Zuberi, A.R., Johnson, K.R., Naggert, J.K., Nishina, P.M. Nat. Genet. (2002) [Pubmed]
  3. Retinal degeneration but not obesity is observed in null mutants of the tubby-like protein 1 gene. Ikeda, S., Shiva, N., Ikeda, A., Smith, R.S., Nusinowitz, S., Yan, G., Lin, T.R., Chu, S., Heckenlively, J.R., North, M.A., Naggert, J.K., Nishina, P.M., Duyao, M.P. Hum. Mol. Genet. (2000) [Pubmed]
  4. A candidate gene for the mouse mutation tubby. Noben-Trauth, K., Naggert, J.K., North, M.A., Nishina, P.M. Nature (1996) [Pubmed]
  5. Glycogen synthase: a putative locus for diet-induced hyperglycemia. Seldin, M.F., Mott, D., Bhat, D., Petro, A., Kuhn, C.M., Kingsmore, S.F., Bogardus, C., Opara, E., Feinglos, M.N., Surwit, R.S. J. Clin. Invest. (1994) [Pubmed]
  6. Polygenic control of Caenorhabditis elegans fat storage. Mak, H.Y., Nelson, L.S., Basson, M., Johnson, C.D., Ruvkun, G. Nat. Genet. (2006) [Pubmed]
  7. Recessive mutations in the gene encoding the tubby-like protein TULP1 in patients with retinitis pigmentosa. Hagstrom, S.A., North, M.A., Nishina, P.L., Berson, E.L., Dryja, T.P. Nat. Genet. (1998) [Pubmed]
  8. Identification and characterization of the mouse obesity gene tubby: a member of a novel gene family. Kleyn, P.W., Fan, W., Kovats, S.G., Lee, J.J., Pulido, J.C., Wu, Y., Berkemeier, L.R., Misumi, D.J., Holmgren, L., Charlat, O., Woolf, E.A., Tayber, O., Brody, T., Shu, P., Hawkins, F., Kennedy, B., Baldini, L., Ebeling, C., Alperin, G.D., Deeds, J., Lakey, N.D., Culpepper, J., Chen, H., Glücksmann-Kuis, M.A., Carlson, G.A., Duyk, G.M., Moore, K.J. Cell (1996) [Pubmed]
  9. Thyroid hormone regulates the obesity gene tub. Koritschoner, N.P., Alvarez-Dolado, M., Kurz, S.M., Heikenwälder, M.F., Hacker, C., Vogel, F., Muñoz, A., Zenke, M. EMBO Rep. (2001) [Pubmed]
  10. A role for the Tubby-like protein 1 in rhodopsin transport. Hagstrom, S.A., Adamian, M., Scimeca, M., Pawlyk, B.S., Yue, G., Li, T. Invest. Ophthalmol. Vis. Sci. (2001) [Pubmed]
  11. G-protein signaling through tubby proteins. Santagata, S., Boggon, T.J., Baird, C.L., Gomez, C.A., Zhao, J., Shan, W.S., Myszka, D.G., Shapiro, L. Science (2001) [Pubmed]
  12. Molecular characterization of TUB, TULP1, and TULP2, members of the novel tubby gene family and their possible relation to ocular diseases. North, M.A., Naggert, J.K., Yan, Y., Noben-Trauth, K., Nishina, P.M. Proc. Natl. Acad. Sci. U.S.A. (1997) [Pubmed]
  13. Mouse model for Usher syndrome: linkage mapping suggests homology to Usher type I reported at human chromosome 11p15. Heckenlively, J.R., Chang, B., Erway, L.C., Peng, C., Hawes, N.L., Hageman, G.S., Roderick, T.H. Proc. Natl. Acad. Sci. U.S.A. (1995) [Pubmed]
  14. Selective up-regulation of fatty acid uptake by adipocytes characterizes both genetic and diet-induced obesity in rodents. Berk, P.D., Zhou, S., Kiang, C., Stump, D.D., Fan, X., Bradbury, M.W. J. Biol. Chem. (1999) [Pubmed]
  15. Cochlear and retinal degeneration in the tubby mouse. Ohlemiller, K.K., Hughes, R.M., Mosinger-Ogilvie, J., Speck, J.D., Grosof, D.H., Silverman, M.S. Neuroreport (1995) [Pubmed]
  16. Evidence of altered hypothalamic pro-opiomelanocortin/ neuropeptide Y mRNA expression in tubby mice. Guan, X.M., Yu, H., Van der Ploeg, L.H. Brain Res. Mol. Brain Res. (1998) [Pubmed]
  17. Characterization of plasma lipids in genetically obese mice: the mutants obese, diabetes, fat, tubby, and lethal yellow. Nishina, P.M., Lowe, S., Wang, J., Paigen, B. Metab. Clin. Exp. (1994) [Pubmed]
  18. Adenosine receptors and modulation of natural killer cell activity by purine nucleosides. Priebe, T., Platsoucas, C.D., Nelson, J.A. Cancer Res. (1990) [Pubmed]
  19. Defective carbohydrate metabolism in mice homozygous for the tubby mutation. Wang, Y., Seburn, K., Bechtel, L., Lee, B.Y., Szatkiewicz, J.P., Nishina, P.M., Naggert, J.K. Physiol. Genomics (2006) [Pubmed]
  20. Localization of insulin-2 (Ins-2) and the obesity mutant tubby (tub) to distinct regions of mouse chromosome 7. Jones, J.M., Meisler, M.H., Seldin, M.F., Lee, B.K., Eicher, E.M. Genomics (1992) [Pubmed]
  21. Strain background effects and genetic modifiers of hearing in mice. Johnson, K.R., Zheng, Q.Y., Noben-Trauth, K. Brain Res. (2006) [Pubmed]
  22. Targeted deletion of the tub mouse obesity gene reveals that tubby is a loss-of-function mutation. Stubdal, H., Lynch, C.A., Moriarty, A., Fang, Q., Chickering, T., Deeds, J.D., Fairchild-Huntress, V., Charlat, O., Dunmore, J.H., Kleyn, P., Huszar, D., Kapeller, R. Mol. Cell. Biol. (2000) [Pubmed]
  23. Cell-specific expression of tubby gene family members (tub, Tulp1,2, and 3) in the retina. Ikeda, S., He, W., Ikeda, A., Naggert, J.K., North, M.A., Nishina, P.M. Invest. Ophthalmol. Vis. Sci. (1999) [Pubmed]
  24. GFP-tagged expression and immunohistochemical studies to determine the subcellular localization of the tubby gene family members. He, W., Ikeda, S., Bronson, R.T., Yan, G., Nishina, P.M., North, M.A., Naggert, J.K. Brain Res. Mol. Brain Res. (2000) [Pubmed]
  25. Caspase-3 inhibitor reduces apototic photoreceptor cell death during inherited retinal degeneration in tubby mice. Bode, C., Wolfrum, U. Mol. Vis. (2003) [Pubmed]
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