Gene Symbol: Tub
Description: tubby bipartite transcription factor
Alias: rd5, tub, tubby protein, retinal degeneration 5, tubby candidate
Species: mouse
Products:     Tub

Top Publications

  1. Schalling M, Johansen J, Nordfors L, Lonnqvist F. Genes involved in animal models of obesity and anorexia. J Intern Med. 1999;245:613-9 pubmed
    ..The role of the Genome Project in developing a complete gene map will greatly facilitate transforming these OTLs to actual molecules involved in the biology of bodyweight. ..
  2. Maddox D, Ikeda S, Ikeda A, Zhang W, Krebs M, Nishina P, et al. An allele of microtubule-associated protein 1A (Mtap1a) reduces photoreceptor degeneration in Tulp1 and Tub Mutant Mice. Invest Ophthalmol Vis Sci. 2012;53:1663-9 pubmed publisher
    To identify genes that modify photoreceptor cell loss in the retinas of homozygous Tulp1(tm1Pjn) and Tub(tub) mice, which exhibit juvenile retinitis pigmentosa. Modifier loci were identified by genetic quantitative trait locus analysis...
  3. Stubdal H, Lynch C, Moriarty A, Fang Q, Chickering T, Deeds J, et al. Targeted deletion of the tub mouse obesity gene reveals that tubby is a loss-of-function mutation. Mol Cell Biol. 2000;20:878-82 pubmed
    ..A positional cloning effort to find the gene responsible for this phenotype led to the identification of tub, a member of a novel gene family of unknown function...
  4. Maddatu T, Naggert J. Allele-specific PCR assays for the tub and cpefat mutations. Mamm Genome. 1997;8:857-8 pubmed
  5. Sun X, Haley J, Bulgakov O, Cai X, McGinnis J, Li T. Tubby is required for trafficking G protein-coupled receptors to neuronal cilia. Cilia. 2012;1:21 pubmed publisher
    ..Thus tubby-like proteins may be generally involved in transciliary trafficking of GPCRs. ..
  6. Heckenlively J, Chang B, Erway L, Peng C, Hawes N, Hageman G, et al. Mouse model for Usher syndrome: linkage mapping suggests homology to Usher type I reported at human chromosome 11p15. Proc Natl Acad Sci U S A. 1995;92:11100-4 pubmed
    ..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...
  7. Caberoy N, Zhou Y, Li W. Tubby and tubby-like protein 1 are new MerTK ligands for phagocytosis. EMBO J. 2010;29:3898-910 pubmed publisher
    ..PPBD was mapped to the highly conserved 54 amino acids at the C-terminal end of tubby and Tulp1. These data suggest that tubby and Tulp1 are novel bridging molecules to facilitate phagocytosis through MerTK. ..
  8. Noben Trauth K, Naggert J, North M, Nishina P. A candidate gene for the mouse mutation tubby. Nature. 1996;380:534-8 pubmed
    A mutation in the tub gene causes maturity-onset obesity, insulin resistance, and sensory deficits...
  9. Kleyn P, Fan W, Kovats S, Lee J, Pulido J, Wu Y, et al. Identification and characterization of the mouse obesity gene tubby: a member of a novel gene family. Cell. 1996;85:281-90 pubmed
    ..A single base change within a splice donor site results in the incorrect retention of a single intron in the mature tub mRNA transcript...

More Information


  1. Hagstrom S, Adamian M, Scimeca M, Pawlyk B, Yue G, Li T. A role for the Tubby-like protein 1 in rhodopsin transport. Invest Ophthalmol Vis Sci. 2001;42:1955-62 pubmed
    ..Comparison of disease phenotypes in the single and double mutants suggests that TULP1 and Tubby are not functionally interchangeable in photoreceptors nor do they form an obligate functional complex. ..
  2. Boggon T, Shan W, Santagata S, Myers S, Shapiro L. Implication of tubby proteins as transcription factors by structure-based functional analysis. Science. 1999;286:2119-25 pubmed
    ..9 angstroms. From primarily structural clues, experiments were devised, the results of which suggest that TULPs are a unique family of bipartite transcription factors. ..
  3. North M, Naggert J, Yan Y, Noben Trauth K, Nishina P. Molecular characterization of TUB, TULP1, and TULP2, members of the novel tubby gene family and their possible relation to ocular diseases. Proc Natl Acad Sci U S A. 1997;94:3128-33 pubmed
    ..Database searches revealed that sequences corresponding to the C terminus of the tub protein were highly conserved across a number of species including humans, mice, Caenorhabditis elegans, ..
  4. Ikeda A, Zheng Q, Zuberi A, Johnson K, Naggert J, Nishina P. Microtubule-associated protein 1A is a modifier of tubby hearing (moth1). Nat Genet. 2002;30:401-5 pubmed
    Once a mutation in the gene tub was identified as the cause of obesity, retinal degeneration and hearing loss in tubby mice, it became increasingly evident that the members of the tub gene family (tulps) influence maintenance and ..
  5. Sahly I, Gogat K, Kobetz A, Marchant D, Menasche M, Castel M, et al. Prominent neuronal-specific tub gene expression in cellular targets of tubby mice mutation. Hum Mol Genet. 1998;7:1437-47 pubmed
    ..The mutated gene, tub , responsible for this phenotype was identified recently, but the function of the TUB protein has not been deduced ..
  6. Coleman D, Eicher E. Fat (fat) and tubby (tub): two autosomal recessive mutations causing obesity syndromes in the mouse. J Hered. 1990;81:424-7 pubmed
    ..syndromes in mice caused by two autosomal recessive mutations, fat (fat), located on chromosome 8, and tubby (tub), located on chromosome 7. Both mutations cause slowly developing but ultimately severe obesity conditions...
  7. Stretton C, Litherland G, Moynihan A, Hajduch E, Hundal H. Expression and modulation of TUB by insulin and thyroid hormone in primary rat and murine 3T3-L1 adipocytes. Biochem Biophys Res Commun. 2009;390:1328-33 pubmed publisher
    b>tub encodes a protein of poorly understood function, but one implicated strongly in the control of energy balance and insulin sensitivity...
  8. Bäckberg M, Madjid N, Ogren S, Meister B. Down-regulated expression of agouti-related protein (AGRP) mRNA in the hypothalamic arcuate nucleus of hyperphagic and obese tub/tub mice. Brain Res Mol Brain Res. 2004;125:129-39 pubmed
    ..The role of the intact tubby protein and the pathogenesis resulting in the phenotype of tub/tub mice remain largely unknown...
  9. Wang Y, Seburn K, Bechtel L, Lee B, Szatkiewicz J, Nishina P, et al. Defective carbohydrate metabolism in mice homozygous for the tubby mutation. Physiol Genomics. 2006;27:131-40 pubmed
    b>Tub is a member of a small gene family, the tubby-like proteins (TULPs), with predominant expression in neurons...
  10. Guan X, Yu H, Van der Ploeg L. Evidence of altered hypothalamic pro-opiomelanocortin/ neuropeptide Y mRNA expression in tubby mice. Brain Res Mol Brain Res. 1998;59:273-9 pubmed
    ..Although the tubby mutation which leads to a splicing defect of the tub gene has been identified recently, the mechanism by which it causes the obesity syndrome has not been established...
  11. Caberoy N, Alvarado G, Li W. Tubby regulates microglial phagocytosis through MerTK. J Neuroimmunol. 2012;252:40-8 pubmed publisher
    ..These results suggest that tubby is a ligand to facilitate microglial phagocytosis through MerTK for the maintenance of CNS homeostasis. ..
  12. Good D, Porter F, Mahon K, Parlow A, Westphal H, Kirsch I. Hypogonadism and obesity in mice with a targeted deletion of the Nhlh2 gene. Nat Genet. 1997;15:397-401 pubmed
    ..Our results support a role for Nhlh2 in the onset of puberty and the regulation of body weight metabolism. ..
  13. Wang F, Tong Q. Transcription factor PU.1 is expressed in white adipose and inhibits adipocyte differentiation. Am J Physiol Cell Physiol. 2008;295:C213-20 pubmed publisher
    ..Furthermore, GATA-2 and PU.1 have an additive inhibitory effect on C/EBP transactivation and adipogenesis. Finally, the expression of PU.1 is increased in white adipose of obese mice. ..
  14. Bouchard G, Johnson D, Carver T, Paigen B, Carey M. Cholesterol gallstone formation in overweight mice establishes that obesity per se is not linked directly to cholelithiasis risk. J Lipid Res. 2002;43:1105-13 pubmed
    ..KK/H1J, NON/LtJ, NOD/LtJ) and five monogenic [carboxypeptidase E (Cpe (fat)), agouti yellow (A(y)), tubby (tub), leptin (Lep(ob)), leptin receptor (Lepr (db))] murine models of obesity during ingestion of a lithogenic diet ..
  15. Petrolonis A, Yang Q, Tummino P, Fish S, Prack A, Jain S, et al. Enzymatic characterization of the pancreatic islet-specific glucose-6-phosphatase-related protein (IGRP). J Biol Chem. 2004;279:13976-83 pubmed
    ..IGRP inhibitors may be an attractive new approach for the treatment of insulin secretion defects in type 2 diabetes. ..
  16. Collins S, Surwit R. Pharmacologic manipulation of ob expression in a dietary model of obesity. J Biol Chem. 1996;271:9437-40 pubmed
  17. Nishina P, Naggert J, Verstuyft J, Paigen B. Atherosclerosis in genetically obese mice: the mutants obese, diabetes, fat, tubby, and lethal yellow. Metabolism. 1994;43:554-8 pubmed
    ..abstract truncated at 250 words) ..
  18. Chung W, Goldberg Berman J, Power Kehoe L, Leibel R. Molecular mapping of the tubby (tub) mutation on mouse chromosome 7. Genomics. 1996;32:210-7 pubmed
    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...
  19. Gao X, Sadana R, Dessauer C, Patel T. Conditional stimulation of type V and VI adenylyl cyclases by G protein betagamma subunits. J Biol Chem. 2007;282:294-302 pubmed
    ..Moreover, Gbetagamma subunits derived from a source(s) other than G(i) are necessary for the full activation of hACVI by isoproterenol in intact cells. ..
  20. Augustine K, Rossi R. Rodent mutant models of obesity and their correlations to human obesity. Anat Rec. 1999;257:64-72 pubmed
    ..In this review, we discuss the physiology and genetics underlying obesity and how studies in rodents and humans are converging, producing a greater understanding of the mechanisms underlying this health problem. ..
  21. Cai X, Chen L, McGinnis J. Correlation of ER stress and retinal degeneration in tubby mice. Exp Eye Res. 2015;140:130-138 pubmed publisher
    Mutation of the Tub gene results in the mislocalization of photoreceptor-specific proteins and eventually retinal degeneration. However, the exact mechanism underlying the retinal degeneration remains largely unknown...
  22. Kim S, Sung H, Lee J, Kim Y, Oh Y, Yoon K, et al. C-terminally mutated tubby protein accumulates in aggresomes. BMB Rep. 2017;50:37-42 pubmed
    The tubby protein (Tub), a putative transcription factor, plays important roles in the maintenance and function of neuronal cells...
  23. Kong L, Li F, Soleman C, Li S, Elias R, Zhou X, et al. Bright cyclic light accelerates photoreceptor cell degeneration in tubby mice. Neurobiol Dis. 2006;21:468-77 pubmed
    ..In the present study, we characterize the kinetics of photoreceptor cell death in Tubby (homozygous tub/tub, which have inherited, progressive retinal degeneration) mice born and raised in a bright cyclic light ..
  24. Warden C, Fisler J, Shoemaker S, Wen P, Svenson K, Pace M, et al. Identification of four chromosomal loci determining obesity in a multifactorial mouse model. J Clin Invest. 1995;95:1545-52 pubmed
    ..These results provide candidate genes and candidate loci for the analysis of human obesity. ..
  25. Nakahara K, Bannai M, Maruyama K, Suzuki Y, Okame R, Murakami N. Characterization of a novel genetically obese mouse model demonstrating early onset hyperphagia and hyperleptinemia. Am J Physiol Endocrinol Metab. 2013;305:E451-63 pubmed publisher
    ..Therefore, the Daruma mice exhibited unique characteristics and may be a good model for studying human metabolic syndrome. ..
  26. Chagnon Y, Bouchard C. Genetics of obesity: advances from rodent studies. Trends Genet. 1996;12:441-4 pubmed
  27. Jones J, Meisler M, Seldin M, Lee B, Eicher E. Localization of insulin-2 (Ins-2) and the obesity mutant tubby (tub) to distinct regions of mouse chromosome 7. Genomics. 1992;14:197-9 pubmed
    ..Analysis of segregation in the F2 generation from the cross C57BL/6J-tub/tub x CAST/Ei demonstrated that Ins-2 and the obesity mutant tubby (tub) are distinct loci, thus eliminating Ins-2 ..
  28. Ikeda A, Naggert J, Nishina P. Genetic modification of retinal degeneration in tubby mice. Exp Eye Res. 2002;74:455-61 pubmed
    Mice that carry the recessive mutation tub develop neurosensory defects including retinal and cochlear degeneration, as well as maturity-onset obesity associated with insulin resistance...
  29. Chang B, Hawes N, Hurd R, Davisson M, Nusinowitz S, Heckenlively J. Retinal degeneration mutants in the mouse. Vision Res. 2002;42:517-25 pubmed
    ..Prph(Rd2)); retinal degeneration 3 (rd3); motor neuron degeneration (mnd); retinal degeneration 4 (Rd4); retinal degeneration 5 (rd5, now tub); vitiligo (vit, now Mitf(mi-vit)); retinal degeneration 6 (rd6); retinal degeneration 7 (..
  30. Ohlemiller K, Hughes R, Lett J, Ogilvie J, Speck J, Wright J, et al. Progression of cochlear and retinal degeneration in the tubby (rd5) mouse. Audiol Neurootol. 1997;2:175-85 pubmed
    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...
  31. Dong Z, Gutierrez Ramos J, Coxon A, Mayadas T, Wagner D. A new class of obesity genes encodes leukocyte adhesion receptors. Proc Natl Acad Sci U S A. 1997;94:7526-30 pubmed
    Obesity is a complex disease, and multiple genes contribute to the trait. The description of five genes (ob, db, tub, Ay, and fat) responsible for distinct syndromes of spontaneous monogenic obesity in mice has advanced our knowledge of ..
  32. Cichutek A, Brueckmann T, Seipel B, Hauser H, Schlaubitz S, Prawitt D, et al. Comparative architectural aspects of regions of conserved synteny on human chromosome 11p15.3 and mouse chromosome 7 (including genes WEE1 and LMO1). Cytogenet Cell Genet. 2001;93:277-83 pubmed
    ..of the genes and markers in both species: "cen-WEE1-D11S2043-ZNF143-RANBP7-CEGF1- ST5-D11S932-LMO1-D11S572-TUB-tel", with inverted order of the murine genes with respect to the telomere/centromere orientation...
  33. Kong L, Tanito M, Huang Z, Li F, Zhou X, Zaharia A, et al. Delay of photoreceptor degeneration in tubby mouse by sulforaphane. J Neurochem. 2007;101:1041-52 pubmed
    In this study, the homozygous tubby (tub/tub) mutant mouse, with an early progressive hearing loss and photoreceptor degeneration, was used as a model system to examine the effects of systemic administration of a naturally occurring ..
  34. Skoulidis F, Cassidy L, Pisupati V, Jonasson J, Bjarnason H, Eyfjord J, et al. Germline Brca2 heterozygosity promotes Kras(G12D) -driven carcinogenesis in a murine model of familial pancreatic cancer. Cancer Cell. 2010;18:499-509 pubmed publisher
    ..We suggest a revised model for tumor suppression by BRCA2 with implications for the therapeutic strategy targeting BRCA2 mutant cancer cells. ..
  35. Keightley P, Morris K, Ishikawa A, Falconer V, Oliver F. Test of candidate gene--quantitative trait locus association applied to fatness in mice. Heredity (Edinb). 1998;81 ( Pt 6):630-7 pubmed
    ..The test is significant for gonadal fat pad weight in males, and gives weak support for an association with the diabetes gene. ..
  36. Caberoy N, Li W. Unconventional secretion of tubby and tubby-like protein 1. FEBS Lett. 2009;583:3057-62 pubmed publisher
    ..Moreover, unconventional secretion of tubby and Tulp1 is independent of endoplasmic reticulum-Golgi pathway. These data implicate that Tulps may function extracellularly as well. ..
  37. Kong L, Zhou X, Li F, Yodoi J, McGinnis J, Cao W. Neuroprotective effect of overexpression of thioredoxin on photoreceptor degeneration in Tubby mice. Neurobiol Dis. 2010;38:446-55 pubmed publisher
    ..Relationships between the Tubby gene, its pathological phenotype and regulation of the thioredoxin system remain to be established. ..
  38. Loktev A, Jackson P. Neuropeptide Y family receptors traffic via the Bardet-Biedl syndrome pathway to signal in neuronal primary cilia. Cell Rep. 2013;5:1316-29 pubmed publisher
    ..Our data demonstrate that ciliary targeting of NPY receptors is important for controlling energy balance in mammals, revealing a physiologically defined ligand-receptor pathway signaling within neuronal cilia. ..
  39. Ohlemiller K, Hughes R, Mosinger Ogilvie J, Speck J, Grosof D, Silverman M. Cochlear and retinal degeneration in the tubby mouse. Neuroreport. 1995;6:845-9 pubmed
    ..Our findings support the tubby mouse as a model of human sensorineural deafness/retinal dystrophic syndrome. Possible human counterparts include Usher's, Alstrom's, and Bardet-Biedl syndromes. ..
  40. Echwald S. Genetics of human obesity: lessons from mouse models and candidate genes. J Intern Med. 1999;245:653-66 pubmed
    ..However, a number of obesity causing genes have successfully been cloned from rodents with monogenic forms of obesity, and it is probable that new knowledge in the field of human obesity will result from these findings. ..
  41. Nishina P, Lowe S, Wang J, Paigen B. Characterization of plasma lipids in genetically obese mice: the mutants obese, diabetes, fat, tubby, and lethal yellow. Metabolism. 1994;43:549-53 pubmed
    ..control strains C57BL/6J (B6) and C57BL/KsJ (BKs) and in the mutants obese (ob), diabetes (db), fat (fat), tubby (tub), and lethal yellow (Ay), which are considered models of non-insulin-dependent diabetes mellitus (NIDDM), to ..
  42. Caberoy N, Maiguel D, Kim Y, Li W. Identification of tubby and tubby-like protein 1 as eat-me signals by phage display. Exp Cell Res. 2010;316:245-57 pubmed publisher
    ..These data reveal a novel activity of tubby and Tulp1, and demonstrate that unbiased identification of eat-me signals by the broadly applicable strategy of ORF phage display can provide detailed insights into phagocyte biology. ..
  43. Stratigopoulos G, Padilla S, LeDuc C, Watson E, Hattersley A, McCarthy M, et al. Regulation of Fto/Ftm gene expression in mice and humans. Am J Physiol Regul Integr Comp Physiol. 2008;294:R1185-96 pubmed publisher
    ..expression was reduced in mesenteric adipose tissue of mice segregating for the Ay, Lep ob, Lepr db, Cpe fat, or tub mutations, and there was a similar trend in other tissues. These effects were not due to adiposity per se...
  44. Rance K, Fustin J, Dalgleish G, Hambly C, Bunger L, Speakman J. A paternally imprinted QTL for mature body mass on mouse chromosome 8. Mamm Genome. 2005;16:567-77 pubmed
  45. Nadeau J. Modifier genes and protective alleles in humans and mice. Curr Opin Genet Dev. 2003;13:290-5 pubmed
    ..Together these modifier genes and protective alleles provide important glimpses into the molecular and cellular basis for the functional networks that provide robustness and homeostasis in complex biological systems. ..
  46. Ohlemiller K, Mosinger Ogilvie J, Lett J, Hughes R, LaRegina M, Olson L. The murine tub (rd5) mutation is not associated with a primary axonemal defect. Cell Tissue Res. 1998;291:489-95 pubmed
    ..Mice homozygous for the tub (rd5) mutation exhibit progressive retinal degeneration, sensorineural hearing loss, reduced fertility, and obesity, and ..
  47. Mukhopadhyay S, Jackson P. Cilia, tubby mice, and obesity. Cilia. 2013;2:1 pubmed publisher
    ..Please see related Research article by Li et al., http://www.ciliajournal.com/content/1/1/21. ..
  48. Chambers D, Wilson L, Alfonsi F, Hunter E, Saxena U, Blanc E, et al. Rhombomere-specific analysis reveals the repertoire of genetic cues expressed across the developing hindbrain. Neural Dev. 2009;4:6 pubmed publisher
    ..These findings give the first genome-wide insight into the complexity of gene expression during patterning of the developing hindbrain. ..
  49. Berk P, Zhou S, Kiang C, Stump D, Fan X, Bradbury M. Selective up-regulation of fatty acid uptake by adipocytes characterizes both genetic and diet-induced obesity in rodents. J Biol Chem. 1999;274:28626-31 pubmed
    ..uptake by adipocytes and hepatocytes from 1) homozygous male obese (ob), diabetic (db), fat (fat), and tubby (tub) mice and from 2) male Harlan Sprague-Dawley rats fed for 7 weeks a diet containing 55% of calories from fat...
  50. Johnson K, Zheng Q, Noben Trauth K. Strain background effects and genetic modifiers of hearing in mice. Brain Res. 2006;1091:79-88 pubmed
    ..The hearing modifier (Moth1) of tubby (Tub(tub)) mutant mice was shown to be a strain variant of the Mtap1a gene...
  51. Xu H, Barnes G, Yang Q, Tan G, Yang D, Chou C, et al. Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance. J Clin Invest. 2003;112:1821-30 pubmed
    ..We propose that obesity-related insulin resistance is, at least in part, a chronic inflammatory disease initiated in adipose tissue. ..