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Transgenic mice with mutations of five aa residues (Lys<jats:sup>523<\/jats:sup>to Gln, Val<jats:sup>524<\/jats:sup>to Leu, Ser<jats:sup>526<\/jats:sup>to Thr, Pro<jats:sup>527<\/jats:sup>to Cys, and Lys<jats:sup>529<\/jats:sup>to Ser), which encompass the ATPase inhibitory determinants located in exon 12, were generated by homologous recombination. Homozygous (\u2212\/\u2212) animals did not develop, but heterozygous (+\/\u2212) mice carrying the expected mutations in the CaD ATPase inhibitory domain (CaD mutant) matured and reproduced normally. The peak force produced in response to KCl and electrical field stimulation by the detrusor smooth muscle from the CaD mutant was high compared with that of the wild type. CaD mutant mice revealed nonvoiding contractions during bladder filling on awake cystometry, suggesting that the CaD ATPase inhibitory domain suppresses force generation during the filling phase and this suppression is partially released by mutations in 50% of CaD in heterozygous. Our data show for the first time a functional phenotype, at the intact smooth muscle tissue and in vivo organ levels, following mutation of a functional domain at the COOH-terminal region of CaD.<\/jats:p>","DOI":"10.1152\/ajprenal.00174.2013","type":"journal-article","created":{"date-parts":[[2013,8,29]],"date-time":"2013-08-29T02:45:03Z","timestamp":1377744303000},"page":"F1455-F1465","source":"Crossref","is-referenced-by-count":5,"title":["Amino acid mutations in the caldesmon COOH-terminal functional domain increase force generation in bladder smooth muscle"],"prefix":"10.1152","volume":"305","author":[{"given":"Maoxian","family":"Deng","sequence":"first","affiliation":[{"name":"Division of Urology, University of Pennsylvania, Glenolden, Pennsylvania;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ettickan","family":"Boopathi","sequence":"additional","affiliation":[{"name":"Division of Urology, University of Pennsylvania, Glenolden, 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