cis-acting determinants of basal and lipid-regulated apolipoprotein A-IV expression in mice.
The levels of apolipoprotein A-IV (apoA-IV) mRNA are regulated by dietary lipid in the liver of both the mouse and rat. Thirteen different inbred mouse strains were fed a high lipid diet, and the effect on apoA-IV liver mRNA levels was examined. It was found that each strain responded in one of two ways. Mice of four strains had higher liver apoA-IV mRNA levels as compared with syngeneic mice fed a normal chow diet. Mice of the other nine strains had decreased liver apoA-IV mRNA levels as compared with syngeneic mice fed a normal chow diet. Using F1 hybrids between mice from BALB/c, C3H, and C57BL/6 and between 129 and C57BL/6, as well as recombinant inbred strains derived from a cross between BALB/c and C57BL/6, we have shown that both the normal level of liver apoA-IV mRNA in the chow-fed mice and the lipid-dependent regulation of apoA-IV mRNA levels are controlled by cis-acting genetic elements. The apoA-IV mRNA levels in mice fed a normal diet varied dramatically among strains, with the largest difference (90-fold) being between the 129/J inbred strain and the C57BL/6J strain. In addition, we have examined the expression of apoA-IV during mouse development. ApoA-IV mRNA is expressed early in mouse liver (16 days postcoitum), whereas others have shown previously that rat liver apoA-IV mRNA is undetectable until 14 days after birth. ApoA-IV mRNA levels in the intestine and apoA-I mRNA levels in the liver and intestine, by contrast, mirror the pattern seen in the rat.
Williams
S C
SC
Department of Human Genetics, Roswell Park Memorial Institute, Buffalo, New York 14263.
Grant
S G
SG
Reue
K
K
Carrasquillo
B
B
Lusis
A J
AJ
Kinniburgh
A J
AJ
D000818:Animals; D001054:Apolipoproteins A / Q000235:genetics*; D015152:Blotting, Northern; D002791:Cholesterol, Dietary / Q000494:pharmacology*; D004041:Dietary Fats / Q000494:pharmacology*; D005786:Gene Expression Regulation; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D008815:Mice, Inbred Strains; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values; D013045:Species Specificity; D014158:Transcription, Genetic / Q000187:drug effects
D001054:Apolipoproteins A; D002791:Cholesterol, Dietary; D004041:Dietary Fats; C022205:apolipoprotein A-IV