| First Author | Harris BS | Year | 2017 |
| Journal | MGI Direct Data Submission | Mgi Jnum | J:237902 |
| Mgi Id | MGI:5817418 | Citation | Harris BS, et al. (2017) Shaky all over: a recessive mutation on Chromosome 13. MGI Direct Data Submission |
| abstractText | The autosomal recessive mutation shaky all over (sao) arose spontaneously in the NOD.Cg-Il10<tm1Cgn>/Dvs strain. By three weeks of age homozygotes exhibit a shaking gait such that they appear to shake all over, and this continues throughout their lifespan. When maintained on the NOD background homozygous for both Il10<tm1Cgn> and sao, they often develop rectal prolapse. Despite a good litter size, maintaining this mutation on this background proved difficult because mothers generally developed rectal prolapse after bearing 1 to 3 litters. The average litter size on this background was 8.59 pups per litter, with 610 pups born in 71 litters. Histological assessment of two homozygotes at 34 weeks of age on this NOD.Cg-Il10<tm1Cgn>/Dvs background found severe Purkinje cell loss in both. The sao mutation was backcrossed onto C57BL/6J. F1 mice were normal, bred, and the percentage of mutants in the F2 generation was as expected for an autosomal recessive mutation. For linkage analysis a CAST/EiJ female was bred with a homozygous male and the F1 offspring were intercrossed to produce F2 progeny. The sao mutation mapped to Chromosome 13 between D13Mit84 and D13Mit19, with eight recombinants among 76 scored meioses unique to each flanking marker and complete concordance with D13Mit241, D13Mit60, D13Mit18, or D13Mit38 out of 100, 102, 102, and 102 meioses assessed, respectively. Whole exome sequencing identified an apparently incidental mutation (GC to CG) occurring within the coding sequence of beta synuclein, Scnb, at Chromosome 13 positions 54,759,932 and 54,759,933 bp (GRCm38), but outside the mapped interval. That mutation is predicted to result in an A102G substitution, changing alanine, a small hydrophobic amino acid, to glycine, a positively charged polar amino acid. Although initial assessment of a targeted null allele of Scnb found no abnormal phenotype, two independent amino acid substitutions in human SCNB have been reported to underlie Lewy body dementia (Ohtake et al., PMID: 15365127). |
