Figure 6.

Chromosome mapping and identification of the gene mutated in r18 mice. (A) Whole-genome linkage analysis suggests that the r18 mutant locus is located on chromosome 19 with a LOD score of 4.6. (B) Fine mapping localizes the r18 locus between marker r18–new9 and the centromere, near the vicinity of the marker D19Mit68, based on the Ensembl Mouse Genome Server. (C) DNA sequencing reveals a single nucleotide insertion (C, in red color) in the Lrp5 gene of the r18 mutant mice, which leads to a frame shift after the 1576th codon of the LRP5 protein. This frame shift is predicted to result in the replacement of the last 39 C-terminal amino acid residues of the LRP5 protein by a new polypeptide of 20 amino acids and a premature termination codon. Amino acid sequence alignment shows that the r18 mutation eliminates the last three of five PPP(S/T)P repeats (labeled in red) at the C-terminus of the LRP5 protein.