Selection of candidate genes for hypertension on rat chromosome 4 from shr using expression profilling in kidney and subcongenic strain development

Using total genome scan, we previously mapped 5 BP‐related QTLs that explain 38% of the BP variance in a progeny derived from Spontaneous Hypertensive Rat (SHR) and Brown Norway (BN) rats. The QTLs were then validated by derivation of congenic strains, including one for chromosome 4 (SHR.BN4) in which a segment from BN replaced the SHR sequences reducing basal systolic BP (~15 mmHg). To select the putative candidate genes, we used genomic approaches based on differential expression in kidney samples and development of subcongenic strains. Sixteen genes were differentially expressed in samples from adult renal tissues from congenic strain SHR.BN4 compared with SHR. Of those, seven remained differentially expressed in the kidney from pre‐hypertensive animals displaying comparable levels of blood pressure. We then verified which of those candidate genes were expressed along the nephron and if they were differentially expressed in mRNA samples from 5 microdissected nephron segments from the two groups. All 7 genes were differentially expressed in one or more of the nephron segments between the 2 strains. Meanwhile, two nonoverlapping congenic substrains were obtained from SHR.BN4, which maintained its phenotype, and one of those harbours 2 of the candidate genes (MGC95152 and Aqp1). Taken together, the combined approaches resulted in selection of 2 hypertensive candidate genes that deserve to be further explored. Supported by FAPESP, CNPq and E.J. Zerbini