| First Author | Longo-Guess CM | Year | 2017 |
| Journal | MGI Direct Data Submission | Mgi Jnum | J:241135 |
| Mgi Id | MGI:5897784 | Citation | Longo-Guess CM, et al. (2017) The variable circling (Varc) mutation. MGI Direct Data Submission |
| abstractText | The variable circling mutation (Varc) arose spontaneously in the C3H/HeJ inbred strain. This mutation is dominant and causes heterozygotes to display head tossing and a mild circling phenotype. The mutants with this phenotype were found to have elevated ABR thresholds compared with their wild-type siblings or C3H/HeJ controls. Histological assessment revealed otitis media in some mutants, but not all, such that the otitis media does not seem required for the elevated ABR thresholds. One mutant was assessed in a swim test and failed to orient in water. Because C3H/HeOuJ is less susceptible to otitis media than C3H/HeJ, which has a missense mutation in TLR4, Varc was backcrossed onto the C3H/HeOuJ background for 9 generations, but no distinct phenotypic differences were detected in the congenic, indicating that otitis media is not the primary lesion in Varc heterozygotes. Two separate mapping crosses were undertaken, one to CAST/EiJ and one to C57BL/6J. In each, a mutant was mated to the inbred mapping strain, selected mutant F1 offspring were backcrossed to C3H/HeJ, these backcross progeny were assessed for the head tossing and circling phenotype, then those deemed Varc/+ and +/+ were genotyped. The Varc phenotype is relatively mild and variable and the phenotype was slightly less pronounced in the CAST/EiJ mapping cross than in the C57BL/6J mapping cross or on a C3H background. The mild and variable phenotype made it difficult to obtain an accurate map position. The mapping cross to CAST/EiJ showed recombination frequencies of 0.0741 (2/27) for D10Mit183, 0.148 (4/27) for D10Mit194, 0.139 (5/36) for D10Mit108, 0,156 (5/32) for D10Mit55, 0.182 (6/33) for D10Mit138, and 0.370 (10/27) for D10Mit95. The mapping cross to C57BL6/J showed recombination frequencies of 0.33 (2/6) for D10Mit3, 0.21 (13/62) for D10Mit194, 0.159 (10/63) for D10Mit130, 0.095 (6/63) for D10Mit115, 0.107 (7/65) for D10Mit42, and 0.38 (11/29) for D10Mit95. Combining these results, the Varc mutation mapped between D10Mit194 (46,844,307 bp, GRCm38) and D10Mit95 (92,502,706 bp, GRCm38) with the possibility that D10Mit138 (53,772,094 bp, GRCm38) is the actual distal marker. Initial efforts at exome sequencing failed to identify the molecular lesion. |
