{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T23:20:15Z","timestamp":1791069615443,"version":"4.1.0"},"reference-count":50,"publisher":"Society for Neuroscience","issue":"24","license":[{"start":{"date-parts":[[2004,12,16]],"date-time":"2004-12-16T00:00:00Z","timestamp":1103155200000},"content-version":"vor","delay-in-days":183,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-sa\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. Neurosci."],"published-print":{"date-parts":[[2004,6,16]]},"abstract":"<jats:p>Mutant mice with a hypersensitive serotonin (5-HT)<jats:sub>3A<\/jats:sub>receptor were generated through targeted exon replacement. A valine to serine mutation (V13\u2032S) in the channel-lining M2 domain of the 5-HT<jats:sub>3A<\/jats:sub>receptor subunit rendered the 5-HT<jats:sub>3<\/jats:sub>receptor \u223c70-fold more sensitive to serotonin and produced constitutive activity when combined with the 5-HT<jats:sub>3B<\/jats:sub>subunit. Mice homozygous for the mutant allele (5-HT<jats:sub>3A<\/jats:sub><jats:sup>vs\/vs<\/jats:sup>) had decreased levels of 5-HT<jats:sub>3A<\/jats:sub>mRNA. Measurements on sympathetic ganglion cells in these mice showed that whole-cell serotonin responses were reduced, and that the remaining 5-HT<jats:sub>3<\/jats:sub>receptors were hypersensitive. Male 5-HT<jats:sub>3A<\/jats:sub><jats:sup>vs\/vs<\/jats:sup>mice died at 2-3 months of age, and heterozygous (5-HT<jats:sub>3A<\/jats:sub><jats:sup>vs\/+<\/jats:sup>) males and homozygous mutant females died at 4-6 months of age from an obstructive uropathy. Both male and female 5-HT<jats:sub>3A<\/jats:sub>mutant mice had urinary bladder mucosal and smooth muscle hyperplasia and hypertrophy, whereas male mutant mice had additional prostatic smooth muscle and urethral hyperplasia. 5-HT<jats:sub>3A<\/jats:sub>mutant mice had marked voiding dysfunction characterized by a loss of micturition contractions with overflow incontinence. Detrusor strips from 5-HT<jats:sub>3A<\/jats:sub><jats:sup>vs\/vs<\/jats:sup>mice failed to contract to neurogenic stimulation, despite overall normal responses to a cholinergic agonist, suggestive of altered neuronal signaling in mutant mouse bladders. Consistent with this hypothesis, decreased nerve fiber immunoreactivity was observed in the urinary bladders of 5-HT<jats:sub>3A<\/jats:sub><jats:sup>vs\/vs<\/jats:sup>compared with 5-HT<jats:sub>3A<\/jats:sub>wild-type (5-HT<jats:sub>3A<\/jats:sub><jats:sup>+\/+<\/jats:sup>) mice. These data suggest that persistent activation of the hypersensitive and constitutively active 5-HT<jats:sub>3A<\/jats:sub>receptor<jats:italic>in vivo<\/jats:italic>may lead to excitotoxic neuronal cell death and functional changes in the urinary bladder, resulting in bladder hyperdistension, urinary retention, and overflow incontinence.<\/jats:p>","DOI":"10.1523\/jneurosci.5658-03.2004","type":"journal-article","created":{"date-parts":[[2004,6,16]],"date-time":"2004-06-16T21:53:13Z","timestamp":1087422793000},"page":"5537-5548","source":"Crossref","is-referenced-by-count":27,"title":["Uropathic Observations in Mice Expressing a Constitutively Active Point Mutation in the 5-HT<sub>3A<\/sub>Receptor Subunit"],"prefix":"10.1523","volume":"24","author":[{"given":"Anindya","family":"Bhattacharya","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Dang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Quan-Ming","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Birthe","family":"Schnegelsberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nora","family":"Rozengurt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gary","family":"Cain","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachelle","family":"Prantil","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David A.","family":"Vorp","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas","family":"Guy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Julius","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony P. 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