Comparative transcriptome analysis of a series of high stepper mutant mice to better understand mutational effect and Rorb function

To better understand the effects of high stepper (hstp) mutations on expression from the Rorb locus, we performed RNAseq on samples of whole brain from WT, Rorbh1/h1, Rorbh2/h2, and Rorbh4/h4 mice. Abnormal transcripts in Rorbh1/h1 brain, mapping upstream of exon 1, likely result from the >326kb duplication in this region, which is thought to cause the hstp phenotype. A similar yet distinct pattern of aberrant transcripts ~150kb farther upstream in Rorbh2/h2 brain may indicate the presence of a different as-yet-undetermined structural mutation in this line. Comparison of all datasets reveals that the dramatic high stepper gait phenotype can occur despite very few changes to the transcriptome of the brain as a whole. Overall design: Brains were harvested from n=3 mice per genotype of WT, Rorbh1/h1, Rorbh2/h2, and Rorbh4/h4 mice, RNA prepared, and RNAseq performed.