| First Author | Gagnon LH | Year | 2017 |
| Journal | MGI Direct Data Submission | Mgi Jnum | J:241422 |
| Mgi Id | MGI:5902449 | Citation | Gagnon LH, et al. (2017) The pvt mutation. MGI Direct Data Submission |
| abstractText | The recessive mutation pivot (pvt) arose spontaneously in the SJL/J strain at The Jackson Laboratory. Homozygotes have a moderate circling phenotype, and complete deafness by 4 weeks of age, the earliest age assessed. This mutation was backcrossed onto the C57BL/6J background and homozygotes were found to have the same phenotypes of circling and complete deafness as assessed by ABR at 4 weeks of age. When 3-month-old homozygotes on the C57BL/6J background were placed in water, two failed to orient at the surface and two were able to swim at the surface, but only in a circular pattern. A 2-month-old homozygote on the SJL/J background also failed to orient in water. While ABR analysis found complete deafness in homozygotes on both SJL/J and C57BL/6J, no hearing loss was detected in heterozgyotes. Mid-modiolar cross sections of whole cochlea from P3 homozygotes on the C57BL/6J congenic background showed a poorly developed stria vascularis. By 1 month of age the stria vascularis had degenerated, the endolymph volume was reduced in the scala media and Reissners membrane had collapsed. Inner ear scanning electron microscopy at P3 additionally revealed regions of hair cell crowding and disorganization from the mid-turn toward the apex. The entire cochlea retains an occasional fourth row of hair cells. Whole mounts of adult inner ears from homozygous mutants showed gross malformations of the semicircular canals. In the process of backcrossing onto C57BL/6J, this mutation was found to segregate within a congenic interval bounded by rs13479533 and rs13479550. Allele tests were run with the Chr 7 mutations twister 4 Jackson (Otog, 29.7 cM), shaker 1 11 Jackson (Myo7a, 53.6 cM), and deaf circler 4 Jackson (Ush1c, 29.7 cM), and none yielded mutants. Mice homozygous for the pvt mutation have inner ear abnormalities similar to those reported in head bobber (hb) homozygotes, and the hb mutation, a 648 bp deletion, is located within the 5.3 Mb pvt candidate region on Chr 7; however, allele tests were not performed because of the difficulty of obtaining mice with the hb mutation. Whole exome sequence analysis failed to identify a causative DNA variant for the pvt phenotype. |
