Atoh1^{tm1(Neurog1)Bfri}

In this knock-in mutation, the coding region of the endogenous gene except for the first 15 base pairs has been replaced by a full-length cDNA encoding mouse neurogenin 1 with an amino-terminal 6X Myc epitope tag, an internal ribosomal entry site (IRES) followed by the coding sequence for the DsRed2 fluorescent protein, and a loxP site-flanked PGK-neo cassette. In homozygous mutant embryos, no Atoh1 expression is detected by in situ hybridization at embryonic day (E) 14.5 or E18.5. Heterozygous embryos exhibit reduced cochlear expression of Atoh1 relative to wild-type littermates. In E14.5 homozygous mutants, Atoh1 promoter-driven Neurog1 expression is observed in vestibular sensory epithelia and the cochlear mid-base; it is expanded in delaminating neuroblasts, as in Atoh1 knock-outs. By E18.5 Neurog1 is detected only in clusters of organ of Corti cells except for continuous expression at the apical tip. Heterozygotes at E14.5 express Neurog1 ectopicaly in vestibular hair cells, while endogenous Neurog1 expression is reduced in delaminating neuroblasts. Atoh1 and Neurog1 are co-expressed in hair cells in E18.5 heterozygotes. (J:242970)