Figure 2. The Lampe1 phenotype is caused by a splice site mutation in Acox1 resulting in deletion of 48 amino-acids from the C-terminal oxidase domain.

(a) Low-resolution mapping of the Lampe1 mutation based on twenty mice and a panel of 359 SNPs covering the entire genome. The Lampe1 phenotype was linked to the distal site of chromosome 11. (b,c) The A→C splice site mutation results in skipping of exon 12 thereby removing 144 nucleotides (b) as determined by amplification and sequencing of the cDNA region covering exon 9–14 (c). (d,e) At the protein level, the mutation causes the deletion of 48 amino-acids from the C-terminal acyl-CoA oxidase C domain (e) resulting in a slightly reduced molecular weight (69.3 kDa instead of a 74.6 kDa protein) (d). Similar differences in molecular weight were observed for liver and kidney tissue.