Abstract
We have previously mapped a diet-induced hypercholesterolemia locus (Dihc2) to chromosome 14 in the F2 generation cross of high-responsive exogenous hypercholesterolemia rats and low-responsive BN rats. To identify a causal gene within this locus, we constructed interval-specific congenic lines and carried out expression and sequencing analyses. Here we narrowed Dihc2 to a region including 33 genes and predicted transcripts and identified RGD1309450_predicted, a homologous gene of SMEK2, as a strong candidate for responsiveness to dietary cholesterol. Our finding provides new insights into the pathway underlying the individual responsiveness to dietary cholesterol in vivo.
Highlights
We have previously mapped a diet-induced hypercholesterolemia locus (Dihc2) to chromosome 14 in the F2 generation cross of high-responsive exogenous hypercholesterolemia rats and low-responsive BN rats
Rats were obtained from KYUDO; ACI/N Slc (ACI), F344/N Slc (F344), and WKY/Izm (WKY/I) rats were from Japan SLC; and WKY/NCrlCrlj (WKY/N) rats were from Japan Charles River
The congenic strains were backcrossed to Exogenously hypercholesterolemia (ExHC) rats for the production of rats with recombinant Dihc2 regions, and recombinant rats were backcrossed to ExHC rats to construct a series of intervalspecific congenic lines (ISCLs)
Summary
We have previously mapped a diet-induced hypercholesterolemia locus (Dihc2) to chromosome 14 in the F2 generation cross of high-responsive exogenous hypercholesterolemia rats and low-responsive BN rats. To identify a causal gene within this locus, we constructed intervalspecific congenic lines and carried out expression and sequencing analyses. We narrowed Dihc to a region including 33 genes and predicted transcripts and identified RGD1309450_predicted, a homologous gene of SMEK2, as a strong candidate for responsiveness to dietary cholesterol. Our finding provides new insights into the pathway underlying the individual responsiveness to dietary cholesterol in vivo.—Asahina, M., W. Identification of SMEK2 as a candidate gene for regulation of responsiveness to dietary cholesterol in rats.
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