Reciprocal hemizygosity analysis of mouse hepatic lipase reveals influence on obesity.
OBJECTIVE
We previously demonstrated coincident quantitative trait loci (QTLs) for percentage body fat, plasma hepatic lipase (HL) activity, and plasma cholesterol on mouse chromosome 7. In the present study, we investigated whether hepatic lipase (Lipc) is an obesity gene, whether Lipc interacts with an unknown gene on chromosome 7, and how HL activity is linked to the chromosome 7 locus.


METHODS
BSB mice are a model of complex obesity due to interactions among genes from C57BL/6J and Mus spretus (SPRET) in (C57BL/6J x SPRET) x C57BL/6J backcross mice. Five crosses tested the impact on obesity of combinations of inactive (knockout) and wild-type Lipc alleles from C57BL/6J or SPRET in a reciprocal hemizygosity analysis.


RESULTS
The combined data from this allelic series suggest that Lipc alleles, and not alleles from a gene linked to Lipc, influence obesity. No interaction between Lipc and chromosome 7 was demonstrated. We confirmed the chromosome 7 QTLs for obesity, HL activity, and cholesterol. Because obesity and HL activity are not consistently associated in the BSB model, linkage of HL activity to chromosome 7 is not secondary to obesity per se. We also report, for the first time to our knowledge, a QTL in mammals for food intake.


CONCLUSIONS
This use of reciprocal hemizygosity analysis in mammals, which, to our knowledge, is the first reported, reveals its power to detect previously unknown effects of Lipc on obesity.
Rowe Program in Genetics, University of California, Davis, California 95616, USA.
Poupak
P
Farahani
Janis S
JS
Fisler
Howard
H
Wong
Adam L
AL
Diament
Nengjun
N
Yi
Craig H
CH
Warden
D000483:Alleles; D000818:Animals; D001483:Base Sequence; D002784:Cholesterol / Q000097:blood; D002874:Chromosome Mapping; D003433:Crosses, Genetic; D004195:Disease Models, Animal; D005260:Female; D008040:Genetic Linkage; D005838:Genotype; D008049:Lipase / Q000235:genetics* / Q000378:metabolism*; D008099:Liver / Q000201:enzymology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D009765:Obesity / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
D002784:Cholesterol; D008049:Lipase