| First Author | Dionne LA | Year | 2015 |
| Journal | MGI Direct Data Submission | Mgi Jnum | J:223793 |
| Mgi Id | MGI:5660417 | Citation | Dionne LA, et al. (2015) Stiffened hindquarters, a new spontaneous mutation. MGI Direct Data Submission |
| abstractText | A mutant phenotype was identified by Amy Leighton in the B6;129S-Gt(ROSA)26Sor<tm38(CAG-GCaMP3)Hze>/J colony at The Jackson Laboratory in late 2013. Homozygotes develop stiffness in the hindquarters with an average age of onset in 12 homozygotes of 62.75 days of age, the earliest appearance at 49 days, and the latest detected at 81 days. The hind legs are stiffened and held much wider than normal and stiffness also develops in the hips. The gait becomes rigid and sometimes hop-like in the hindquarters although the front legs appear to move in the normal alternating manner without noticeable stiffness. We have named this mutation stiffened hindquarters, with the mutation symbol stiff. This stiffening of the hindquarters is progressive, but does not become crippling and homozygotes are able to move reasonably, access the food hopper and water bottle, and reproduce. Both males and females will reproduce after phenotypic onset and homozygous females have taken care of their litters. One female homozygote at 6 weeks of age and one female homozygote at five and a half weeks of age, along with aged matched controls, were assessed for their ability to swim and both were able to swim. No noteworthy lesions were identified in a standard pathological assessment of one homozygous male at 34 weeks of age and one homozygous male at 6 weeks of age. Ophthalmoscopy found no defects in the eyes of one male or 2 female homozygotes at 7 weeks of age. A mapping outcross to FVB/NJ generating 20 mutants and 17 unaffected littermates in the F2 population had only 2 recombinants with rs3687890 at Chromosome 11 position 112355670 bp linking this mutation to distal Chromosome 11. Whole exome sequencing identified two unique variants tightly linked on proximal Chromosome 11: a missense mutation in ferredoxin reductase (Fdxr) and a mutation in the 5 UTR of otopetrin 3 (Otop3). The mutation in Fdxr is a C to T SNV at Chromosome 11 position 115,269,462 bp (GRCm38) resulting in the codon change cGg/cAg and the resulting amino acid change R389Q. The mutation in the 5 UTR of Otop3 is a G to A change at Chromosome 11 position 115,332,175 bp (GRCm38) with unknown consequence. Of 36 mutants typed, all had both mutations, of 37 heterozygotes all typed as heterozygous for both mutations, and the remaining 18 unaffected siblings all typed wild type for both genes. No mouse from a heterozygote x heterozygote intercross had only one or the other mutation. |
