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Although surgical resection of the aganglionic segment allows <jats:styled-content style=\"fixed-case\">HSCR<\/jats:styled-content> children to survive this condition, a number of patients still suffer from impaired motility despite having myenteric ganglia in their postoperative distal bowel. Such phenomenon is also observed in patients suffering from other enteric neuropathies and, in both cases, colonic dysmotility is believed to result from abnormalities of myenteric ganglia and\/or associated interstitial cells of Cajal (<jats:styled-content style=\"fixed-case\">ICC<\/jats:styled-content>). To better understand this, we used a recently described <jats:styled-content style=\"fixed-case\">HSCR<\/jats:styled-content> mouse model called <jats:italic>TashT<\/jats:italic>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Intestinal motility parameters were assessed and correlated with extent of aganglionosis and with neuronal density in ganglionated regions. The neural composition of the myenteric plexus and the status of <jats:styled-content style=\"fixed-case\">ICC<\/jats:styled-content> networks was also evaluated using immunofluorescence.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p><jats:italic>TashT<\/jats:italic><jats:sup>Tg\/Tg<\/jats:sup> mice display a strong male bias in the severity of both colonic aganglionosis and hypoganglionosis, which are associated with male\u2010specific reduced colonic motility. <jats:italic>TashT<\/jats:italic><jats:sup>Tg\/Tg<\/jats:sup> male mice also exhibit a specific increase in nNos<jats:sup>+<\/jats:sup> neurons that is restricted to the most distal ganglionated regions. In contrast, Calretinin<jats:sup>+<\/jats:sup> myenteric neurons, Sox10<jats:sup>+<\/jats:sup> myenteric glial cells, and cKit<jats:sup>+<\/jats:sup> <jats:styled-content style=\"fixed-case\">ICC<\/jats:styled-content> are not affected in <jats:italic>TashT<\/jats:italic><jats:sup>Tg\/Tg<\/jats:sup> mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions and Inferences<\/jats:title><jats:p>Male\u2010specific impairment of colonic motility in <jats:italic>TashT<\/jats:italic><jats:sup>Tg\/Tg<\/jats:sup> mice is associated with both severe hypoganglionosis and myenteric neuronal imbalance. Considering these parameters in the clinic might be important for the management of postoperative <jats:styled-content style=\"fixed-case\">HSCR<\/jats:styled-content> patients.<\/jats:p><\/jats:sec>","DOI":"10.1111\/nmo.12847","type":"journal-article","created":{"date-parts":[[2016,6,9]],"date-time":"2016-06-09T01:57:01Z","timestamp":1465437421000},"page":"1494-1507","source":"Crossref","is-referenced-by-count":15,"title":["Male\u2010specific colon motility dysfunction in the <i>TashT<\/i> mouse line"],"prefix":"10.1111","volume":"28","author":[{"given":"A. 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