Positional identification of Adamts16 variants linked to inherited hypertension: gene expression of congenic vs S rats

We used Affymetrix GeneChips to expression profile kidneys from Dahl salt-senstive hypertensive inbred strain and less hypertensive S.LEW(D1MCO4x1x3Bx1) congenic strain to identify genes downstream of Adamts16 (the function of Adamts16 has yet to be fully delineated). The S.LEW(D1MCO4x1x3Bx1) congenic animal is an S rat containing the LEWIS allele for Adamts16 instead of the S allele. It is hypothesized that allelic differences in Adamts16 in inbred rats is responsible for blood pressure variance. We further hypothesize that gene expression differences in the kidneys of S.LEW(D1MCO4x1x3Bx1) versus S result from sequence differences between the S and LEWIS alleles of Adamts16. Lastly, the downstream genes differentially regulated by the Adamts16 alleles may provide insight pertaining to the mechanism of blood pressure differences. Gene expression differences resulting from these kidney comparisons will be compared to the gene expression profiling experiments comparing siRNA-mediated knockdown of Adamts16 in NRK-52E kidney cells versus scrambled siRNA control.

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Joe B, Saad Y, Dhindaw S, Lee NH, Frank BC, Achinike OH, Luu TV, Gopalakrishnan K, Toland EJ, Farms P, Yerga-Woolwine S, Manickavasagam E, Rapp JP, Garrett MR, Coe D, Apte SS, Rankinen T, Pérusse L, Ehret GB, Ganesh SK, Cooper RS, O'Connor A, Rice T, Weder AB, Chakravarti A, Rao DC, Bouchard C