Ret (ret proto-oncogene) is a common receptor for the glial-derived neurotrophic factor (GDNF) family of ligands that is highly expressed in nonpeptidergic neurons as well as many other cell types.
Exons 14 and 15 are flanked by loxP sites in this Retfl targeted mutant strain. A V805A mutation in exon 15 is functionally silent, but sensitizes the protein to chemical inhibition of its kinase activity; signaling should be blocked by 1NMPP1 (unpublished). Cre-mediated excision of the floxed region results in a knockout allele.
When crossed with Wnt1-Cre mice, RET expression is undetectable in dorsal root ganglia (DRG), indicating efficient cre-mediated excision of the floxed region. Within 3 days of birth the compound mutant mice show abdominal distension, progressive weakness, and few survive beyond 3 weeks of age. Examination at postnatal day 14 (P14) reveals that they have an enlarged jejunum, ileum, and colon, suggesting that they may have intestinal aganglionosis similar to human patients carrying RET mutations who develop Hirschsprung's disease.
