| First Author | Jain S | Year | 2004 |
| Journal | Development | Volume | 131 |
| Issue | 21 | Pages | 5503-13 |
| PubMed ID | 15469971 | Mgi Jnum | J:93262 |
| Mgi Id | MGI:3056701 | Doi | 10.1242/dev.01421 |
| Citation | Jain S, et al. (2004) Mice expressing a dominant-negative Ret mutation phenocopy human Hirschsprung disease and delineate a direct role of Ret in spermatogenesis. Development 131(21):5503-13 |
| abstractText | The Ret receptor tyrosine kinase mediates physiological signals of glial cell line-derived neurotrophic factor (GDNF) family ligands (GFLs) and is essential for postnatal survival in mice. It is implicated in a number of human diseases and developmental abnormalities. Here, we describe our analyses of mice expressing a Ret mutant (RetDN) with diminished kinase activity that inhibits wild-type Ret activity, including its activation of AKT. All Ret(DN/+) mice died by 1 month of age and had distal intestinal aganglionosis reminiscent of Hirschsprung disease (HSCR) in humans. The Ret(DN/+) 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 Ret(DN/+) mice only had defects in the parasympathetic nervous system. A small proportion of Ret(DN/+) 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. |
