Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2002-4-1
pubmed:abstractText
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 function of the neuronal cell lineage. Suggested molecular functions of tubby-like proteins include roles in vesicular trafficking, mediation of insulin signaling and gene transcription. The mechanisms through which tub functions in neurons, however, have yet to be elucidated. Here we report the positional cloning of an auditory quantitative trait locus (QTL), the modifier of tubby hearing 1 gene (moth1), whose wildtype alleles from strains AKR/J, CAST/Ei and 129P2/OlaHsd protect tubby mice from hearing loss. Through a transgenic rescue experiment, we verified that sequence polymorphisms in the neuron-specific microtubule-associated protein 1a gene (Mtap1a) observed in the susceptible strain C57BL/6J (B6) are crucial for the hearing-loss phenotype. We also show that these polymorphisms change the binding efficiency of MTAP1A to postsynaptic density molecule 95 (PSD95), a core component in the cytoarchitecture of synapses. This indicates that at least some of the observed polymorphisms are functionally important and that the hearing loss in C57BL/6J-tub/tub (B6-tub/tub) mice may be caused by impaired protein interactions involving MTAP1A. We therefore propose that tub may be associated with synaptic function in neuronal cells.
pubmed:grant
pubmed:commentsCorrections
http://linkedlifedata.com/resource/pubmed/commentcorrection/11925566-10380929, http://linkedlifedata.com/resource/pubmed/commentcorrection/11925566-10441341, http://linkedlifedata.com/resource/pubmed/commentcorrection/11925566-10455176, http://linkedlifedata.com/resource/pubmed/commentcorrection/11925566-10509669, http://linkedlifedata.com/resource/pubmed/commentcorrection/11925566-10549638, http://linkedlifedata.com/resource/pubmed/commentcorrection/11925566-10591637, http://linkedlifedata.com/resource/pubmed/commentcorrection/11925566-10607826, http://linkedlifedata.com/resource/pubmed/commentcorrection/11925566-10629044, http://linkedlifedata.com/resource/pubmed/commentcorrection/11925566-10996791, http://linkedlifedata.com/resource/pubmed/commentcorrection/11925566-11212298, http://linkedlifedata.com/resource/pubmed/commentcorrection/11925566-11375483, http://linkedlifedata.com/resource/pubmed/commentcorrection/11925566-11406614, http://linkedlifedata.com/resource/pubmed/commentcorrection/11925566-11481257, http://linkedlifedata.com/resource/pubmed/commentcorrection/11925566-11925554, http://linkedlifedata.com/resource/pubmed/commentcorrection/11925566-7479945, http://linkedlifedata.com/resource/pubmed/commentcorrection/11925566-8606774, http://linkedlifedata.com/resource/pubmed/commentcorrection/11925566-8612280, http://linkedlifedata.com/resource/pubmed/commentcorrection/11925566-9425894, http://linkedlifedata.com/resource/pubmed/commentcorrection/11925566-9786987, http://linkedlifedata.com/resource/pubmed/commentcorrection/11925566-9916795
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/DNA, Complementary, http://linkedlifedata.com/resource/pubmed/chemical/Dlgh4 protein, mouse, http://linkedlifedata.com/resource/pubmed/chemical/Genetic Markers, http://linkedlifedata.com/resource/pubmed/chemical/Guanylate Kinase, http://linkedlifedata.com/resource/pubmed/chemical/Insulin, http://linkedlifedata.com/resource/pubmed/chemical/Intracellular Signaling Peptides..., http://linkedlifedata.com/resource/pubmed/chemical/Membrane Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Microtubule-Associated Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Mtap1a protein, mouse, http://linkedlifedata.com/resource/pubmed/chemical/Nerve Tissue Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Tub protein, mouse, http://linkedlifedata.com/resource/pubmed/chemical/postsynaptic density proteins
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
1061-4036
pubmed:author
pubmed:issnType
Print
pubmed:volume
30
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
401-5
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed-meshheading:11925566-Alleles, pubmed-meshheading:11925566-Animals, pubmed-meshheading:11925566-Cell Line, pubmed-meshheading:11925566-Cloning, Molecular, pubmed-meshheading:11925566-DNA, Complementary, pubmed-meshheading:11925566-Gene Library, pubmed-meshheading:11925566-Genetic Markers, pubmed-meshheading:11925566-Guanylate Kinase, pubmed-meshheading:11925566-Immunoblotting, pubmed-meshheading:11925566-Insulin, pubmed-meshheading:11925566-Intracellular Signaling Peptides and Proteins, pubmed-meshheading:11925566-Membrane Proteins, pubmed-meshheading:11925566-Mice, pubmed-meshheading:11925566-Mice, Inbred C57BL, pubmed-meshheading:11925566-Mice, Transgenic, pubmed-meshheading:11925566-Microscopy, Fluorescence, pubmed-meshheading:11925566-Microtubule-Associated Proteins, pubmed-meshheading:11925566-Models, Genetic, pubmed-meshheading:11925566-Nerve Tissue Proteins, pubmed-meshheading:11925566-Neurons, pubmed-meshheading:11925566-Phenotype, pubmed-meshheading:11925566-Polymorphism, Genetic, pubmed-meshheading:11925566-Precipitin Tests, pubmed-meshheading:11925566-Protein Binding, pubmed-meshheading:11925566-Protein Structure, Tertiary, pubmed-meshheading:11925566-Proteins, pubmed-meshheading:11925566-Quantitative Trait, Heritable, pubmed-meshheading:11925566-Reverse Transcriptase Polymerase Chain Reaction, pubmed-meshheading:11925566-Signal Transduction, pubmed-meshheading:11925566-Synapses, pubmed-meshheading:11925566-Transcription, Genetic, pubmed-meshheading:11925566-Transgenes
pubmed:year
2002
pubmed:articleTitle
Microtubule-associated protein 1A is a modifier of tubby hearing (moth1).
pubmed:affiliation
The Jackson Laboratory, 600 Main Street, Bar Harbor, Maine 04609, USA.
More...