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The RetDN\/+ proximal small intestine also had severe hypoganglionosis and reduction in nerve fiber density, suggesting a potential mechanism for the continued gastric dysmotility in postsurgical HSCR patients. Unlike Ret-null mice, which have abnormalities in the parasympathetic and sympathetic nervous systems, the RetDN\/+ mice only had defects in the parasympathetic nervous system. A small proportion of RetDN\/+ mice had renal agenesis, and the remainder had hypoplastic kidneys and developed tubulocystic abnormalities postnatally. Postnatal analyses of the testes revealed a decreased number of germ cells, degenerating seminiferous tubules,maturation arrest and apoptosis, indicating a crucial role for Ret in early spermatogenesis.<\/jats:p>","DOI":"10.1242\/dev.01421","type":"journal-article","created":{"date-parts":[[2004,10,7]],"date-time":"2004-10-07T00:13:55Z","timestamp":1097108035000},"page":"5503-5513","source":"Crossref","is-referenced-by-count":113,"title":["Mice expressing a dominant-negative Ret mutation phenocopy human Hirschsprung disease and delineate a direct role of Ret in spermatogenesis"],"prefix":"10.1242","volume":"131","author":[{"given":"Sanjay","family":"Jain","sequence":"first","affiliation":[{"name":"Department of Pathology and Immunology, Washington University School of Medicine, 660 South Euclid Avenue, St Louis, MO 63110, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cathy K.","family":"Naughton","sequence":"additional","affiliation":[{"name":"Department of Urologic Surgery, Washington University School of Medicine, 660 South Euclid Avenue, St Louis, MO 63110, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mao","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Pathology and Immunology, Washington University School of Medicine, 660 South Euclid Avenue, St Louis, MO 63110, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy","family":"Strickland","sequence":"additional","affiliation":[{"name":"Department of Urologic Surgery, Washington University School of Medicine, 660 South Euclid Avenue, St Louis, MO 63110, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kiran","family":"Vij","sequence":"additional","affiliation":[{"name":"Department of Pathology and Immunology, Washington University School of Medicine, 660 South Euclid Avenue, St Louis, MO 63110, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mario","family":"Encinas","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Pharmacology, Washington University School of Medicine, 660 South Euclid Avenue, St Louis, MO 63110, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Judy","family":"Golden","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Pharmacology, Washington University School of Medicine, 660 South Euclid Avenue, St Louis, MO 63110, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akshay","family":"Gupta","sequence":"additional","affiliation":[{"name":"Department of Urologic Surgery, Washington University School of Medicine, 660 South Euclid Avenue, St Louis, MO 63110, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Heuckeroth","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Washington University School of Medicine, 660 South Euclid Avenue, St Louis, MO 63110, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr","given":"Eugene M.","family":"Johnson","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Pharmacology, Washington University School of Medicine, 660 South Euclid Avenue, St Louis, MO 63110, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey","family":"Milbrandt","sequence":"additional","affiliation":[{"name":"Department of Pathology and Immunology, Washington University School of Medicine, 660 South Euclid Avenue, St Louis, MO 63110, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","reference":[{"key":"2021042604460075300_REF1","doi-asserted-by":"crossref","unstructured":"Airaksinen, M. 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Renal agenesis and the absence of enteric neurons in mice lacking GDNF. Nature382, 70-73.","DOI":"10.1038\/382070a0"},{"key":"2021042604460075300_REF41","doi-asserted-by":"crossref","unstructured":"Sariola, H. and Saarma, M. (2003). Novel functions and signalling pathways for GDNF. J. Cell Sci.116,3855-3862.","DOI":"10.1242\/jcs.00786"},{"key":"2021042604460075300_REF42","doi-asserted-by":"crossref","unstructured":"Schuchardt, A., D'Agati, V., Larsson-Blomberg, L., Costantini,F. and Pachnis, V. (1994). Defects in the kidney and enteric nervous system of mice lacking the tyrosine kinase receptor Ret. Nature367,380-383.","DOI":"10.1038\/367380a0"},{"key":"2021042604460075300_REF43","doi-asserted-by":"crossref","unstructured":"Schuchardt, A., D'Agati, V., Pachnis, V. and Costantini, F.(1996). Renal agenesis and hypodysplasia in ret-k-mutant mice result from defects in ureteric bud development. Development122,1919-1929.","DOI":"10.1242\/dev.122.6.1919"},{"key":"2021042604460075300_REF44","doi-asserted-by":"crossref","unstructured":"Shimotake, T., Go, S., Inoue, K., Tomiyama, H. and Iwai, N.(2001). A homozygous missense mutation in the tyrosine kinase domain of the RET proto-oncogene in an infant with total intestinal aganglionosis. Am. J. Gastroenterol.96,1286-1291.","DOI":"10.1111\/j.1572-0241.2001.03714.x"},{"key":"2021042604460075300_REF45","doi-asserted-by":"crossref","unstructured":"Shimotake, T., Tomiyama, H., Aoi, S. and Iwai, N.(2003). Discrepancy between macroscopic and microscopic transitional zones in Hirschsprung[apos]s disease with reference to the type of RET\/GDNF\/SOX10 gene mutation. J. Pediatr. Surg.38,698-701.","DOI":"10.1016\/jpsu.2003.50186"},{"key":"2021042604460075300_REF46","doi-asserted-by":"crossref","unstructured":"Solari, V., Ennis, S., Yoneda, A., Wong, L., Messineo, A.,Hollwarth, M. E., Green, A. and Puri, P. (2003). 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