| First Author | Harris BS | Year | 2016 |
| Journal | MGI Direct Data Submission | Mgi Jnum | J:236909 |
| Mgi Id | MGI:5810185 | Citation | Harris BS, et al. (2016) Jimpy 6 Jackson. MGI Direct Data Submission |
| abstractText | An X-linked neurological mutation arose spontaneously in the BALB/cJ inbred strain at The Jackson Laboratory. By three weeks of age hemizygous males exhibited a shaky gait such that they appeared to shake all over, and this continued throughout their shortened lifespan. Very few males survived beyond eight weeks, those that did died soon after, and none bred so the strain was maintained by breeding proven carrier females to wild-type males at each generation. Heterozygous females appear unaffected. When used for in vitro fertilization, sperm cryopreserved from an eight-week-old hemizygote failed to fertilize any eggs. Sperm from two six-week-old hemizygotes was harvested for cryopreservation, but was found to have no motility at all and the sperm counts were very low, less than a quarter the expected number. From the heterozygote x wildtype breeding scheme 107 hemizygous males were identified out of 526 total pups, of which 2 were born dead and 9 were missing or found dead prior to phenotypic assessment. Even if the 11 pups that were not phenotyped are assumed to have been hemizygotes, there is either incomplete penetrance, or, more likely, in utero death of a small percentage of hemizygotes. To map this mutation, a heterozygous female was bred to a C57BL/6NJ male and two unaffected male offspring were bred to their unaffected female siblings and SNP analysis of 13 affected male offspring showed clear linkage with Chromosome X with only one recombinant for rs3706437, at 121,686,916 bp, and rs3702256, at 134,949,219 bp, and 2 recombinants for rs3723498 at 144,314,241 bp. Exome sequencing identified a single nucleotide variant, C to G, on Chromosome X at 136,832,207 bp (GRCm38), which is predicted to result in the missense mutation P149R in Proteolipid protein (myelin) 1 (Plp1). Genotyping for this allele was consistent with phenotype: four hemizygous males had the G SVN, 2 wild-type males C, and one heterozygous female also had the G SNV. As the sixth spontaneous mutation in the Plp1 gene to arise and be characterized at The Jackson Laboratory this spontaneous SNV has been designated jimpy 6 Jackson Plp1<jp-6J>. |
