| First Author | Harris BS | Year | 2015 |
| Journal | MGI Direct Data Submission | Mgi Jnum | J:224655 |
| Mgi Id | MGI:5688518 | Citation | Harris BS, et al. (2015) The malformed digits 3 Jackson mutation. MGI Direct Data Submission |
| abstractText | The malformed digits 3 Jackson (mdig-3J) mutation causes shortened or fused digits on all four feet, with some toes being both shortened and fused. Mutants are slightly smaller than normal littermates and although the teeth require trimming when the mutants are young, this need often goes away as the mice mature. Some homozygotes fail to breed, but homozygous females breed sufficiently to maintain the strain with homozygous x heterozygous breeder pairs. The mdig-3J mutation arose spontaneously in the B6.129-Reg3g<tm1.1Lvh>/J strain at The Jackson Laboratory. As the targeted mutation was bred out of this mutant subline by backcrossing to C57BL/6J, the mdig-3J phenotype remained the same. Outcrossing a mutant female to C57BL/6J or FVB/NJ failed to produce mutant offspring in the F1 population but did, in both cases, in the F2 population, proving that this mutation is recessive. The FVB/NJ F2 population was used for mapping. SNP analysis found no recombination between mdig-3J and rs3682381 in any of 10 homozygotes. Exome sequencing subsequently identified a C to T transition on Chromosome 2 at position 91,492,644 that is predicted to result in the codon change CGG to TGG and subsequent R1158W missense mutation in low density lipoprotein receptor-related protein 4 (Lrp4). This non-conserved amino acid substitution falls within the third of the four TolB-like six-bladed beta-propeller domains. This point mutation provides a valuable variant for correlating specific mutations in the third beta-propeller domain with phenotypes of Cenani-Lenz syndactyly syndrome and sclerosteosis 2. |
