Mapping Data

Experiment

• Experiment
  TEXT
• Chromosome
  4
• Reference
  J:75358 Koishi R, et al., Angptl3 regulates lipid metabolism in mice. Nat Genet. 2002 Feb;30(2):151-7
• ID
  MGI:2384030

Genes

Gene	Assay Type
Angptl3	visible phenotype
D4Mit255
D4Mit58

Notes

• Experiment
  A locus linked to hypolipidemia (hypl) was mapped to mouse Chromosome 4 with a LOD score of 25.89 at D4Mit255 and D4Mit58 using a (KK/Snk x BALB/c)F1 x KK/Snk backcross. Parental strain KK/Snk, a substrain of KK, exhibits recessively inherited hypolipidemia whereas parental strain BALB/c is normolipidemic. Chromosome walking starting at D4Mit255 localized hypl to a 600 kb region representedy by a BAC contig. Screening of candidate genes revealed that expression of Angptl3 is 1/30-1/40 that of wild type KK mice. Sequence analysis of Angptl3 mRNA from KK/Snk mice revealed a 4 bp insertion in exon 6 that results in a stop codon at position 347. This mutation does not exist in mRNA from BALB/c, CBA, C3H/He, DBA, and NC wild type strains. Injection of recombinant adenovirus vectors carrying either mouse Angptl3 or human ANGPTL3 into KK/Snk animals resulted in temporary rescue of hypolipidemia by raising plasma lipid levels. Authors believe Angptl3 is the gene responsible for the hypolipidemic phenotype observed in KK/Snk animals.