A polymorphism in New Zealand inbred mouse strains that inactivates phosphatidylcholine transfer protein.
New Zealand obese (NZO/HlLt) male mice develop polygenic diabetes and altered phosphatidylcholine metabolism. The gene encoding phosphatidylcholine transfer protein (PC-TP) is sited within the support interval for Nidd3, a recessive NZO-derived locus on Chromosome 11 identified by prior segregation analysis between NZO/HlLt and NON/Lt. Sequence analysis revealed that the NZO-derived PC-TP contained a non-synonymous point mutation that resulted in an Arg120His substitution, which was shared by the related NZB/BlNJ and NZW/LacJ mouse strains. Consistent with the structure-based predictions, functional studies demonstrated that Arg120His PC-TP was inactive, suggesting that this mutation contributes to the deficiencies in phosphatidylcholine metabolism observed in NZO mice.
Pan
Huei-Ju
HJ
Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
Agate
Diana S
DS
King
Benjamin L
BL
Wu
Michele K
MK
Roderick
Steven L
SL
Leiter
Edward H
EH
Cohen
David E
DE
D019943:Amino Acid Substitution; D000818:Animals; D001483:Base Sequence; D002874:Chromosome Mapping; D018076:DNA, Complementary / Q000235:genetics; D008297:Male; D051379:Mice; D008814:Mice, Inbred NZB / Q000235:genetics*; D008815:Mice, Inbred Strains; D008820:Mice, Obese / Q000235:genetics* / Q000378:metabolism; D008958:Models, Molecular; D010713:Phosphatidylcholines / Q000378:metabolism; D049294:Phospholipid Transfer Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000235:genetics*; D017354:Point Mutation; D011110:Polymorphism, Genetic; D011487:Protein Conformation; D013045:Species Specificity
D018076:DNA, Complementary; D010713:Phosphatidylcholines; D049294:Phospholipid Transfer Proteins