A spontaneous mouse deletion in Mctp1 uncovers a long-range cis-regulatory region crucial for NR2F1 function during inner ear development.

Basile Tarchini, The Jackson Laboratory
Chantal M. Longo-Guess, The Jackson Laboratory
Cong Tian, The Jackson Laboratory
Abby Tadenev, The Jackson Laboratory
Nicholas Devanney, The Jackson Laboratory
Kenneth R. Johnson, The Jackson Laboratory

We thank Melissa Berry and Vidhya Munnamalai for their helpful comments on the manuscript and the Jackson Laboratory's Reproductive Sciences Services for cryopreservation of newly developed inbred strains and importation and recovery of cryopreserved lines.


Hundreds of thousands of cis-regulatory DNA sequences are predicted in vertebrate genomes, but unlike genes themselves, few have been characterized at the functional level or even unambiguously paired with a target gene. Here we serendipitously identified and started investigating the first reported long-range regulatory region for the Nr2f1 (Coup-TFI) transcription factor gene. NR2F1 is temporally and spatially regulated during development and required for patterning and regionalization in the nervous system, including sensory hair cell organization in the auditory epithelium of the cochlea. Analyzing the deaf wanderer (dwnd) spontaneous mouse mutation, we traced back the cause of its associated circling behavior to a 53 kb deletion removing five exons and adjacent intronic regions of the poorly characterized Mctp1 gene. Interestingly, loss of Mctp1 function cannot account for the hearing loss, inner ear dysmorphology and sensory hair cell disorganization observed in dwnd mutants. Instead, we found that the Mctp1