Rorc^m1Btlr

The chestnut mutation is a T to C transition at base pair 94,377,609 (v38) on chromosome 3 within the linear genomic DNA sequence of Rorc (GenBank genomic region NC_000069). The mutation affects the intron 1 donor splice site of the Rorc splice variant encoding Rorgamma (GTAAGT-->GTAAGC; ENSMUST00000107292), but has no effect on the splice variant encoding Rorgamma1. The effects of the mutation at the cDNA and protein level have not been tested, but weakening of the intron 1 donor splice site may result in retention of intron 1 in the spliced mRNA. Alternatively, utilization of cryptic splice site(s) may occur. One specific possibility is splicing from a cryptic splice donor site in the 5' UTR to the normal splice acceptor site in intron 1, resulting in skipping of exon 1 and removal of the normal ATG translation start site in the Rorgammat mRNA (see the sections, below, for more information about the Rorgamma isoforms). An alternative ATG is present in exon 3. Use of this start would frame-shift the protein and result in truncation of the protein 87 amino acids following the methionine start site (within exon 4). This model was generated at UT Southwestern Medical Center at Dallas. (J:203039)