Hypertension in humans and experimental models has a strong hereditary basis, but identification of causative genes remains challenging. Quantitative trait loci (QTLs) for hypertension and salt sensitivity have been reported on rat chromosome 18. We set out to genetically isolate and prioritize genes within the salt-sensitivity and hypertension QTLs on the spontaneously hypertensive rat (SHR) chromosome 18 by developing and characterizing a series of congenic strains derived from the SHR and normotensive Brown Norway rat strains. The SHR.BN-D18Rat113/D18Rat82 congenic strain exhibits significantly lower blood pressure and is salt resistant compared with the SHR. Transplantation of kidneys from SHR.BN-D18Rat113/D18Rat82 donors into SHR recipients is sufficient to attenuate increased blood pressure but not salt sensitivity. Derivation of congenic sublines allowed for the separation of salt sensitivity from hypertension QTL regions. Renal expression studies with microarray and Solexa-based sequencing in parental and congenic strains identified 4 differentially expressed genes within the hypertension QTL region, one of which is an unannotated transcript encoding a previously undescribed, small, nonprotein coding RNA. Sequencing selected biological candidate genes within the minimal congenic interval revealed a nonsynonymous variant in SHR transcription factor 4. The minimal congenic interval is syntenic to a region of human chromosome 18 where significant linkage to hypertension was observed in family based linkage studies. These congenic lines provide reagents for identifying causative genes that underlie the chromosome 18 SHR QTLs for hypertension and salt sensitivity. Candidate genes identified in these studies merit further investigation as potentially causative hypertension genes in SHR and human hypertension.

• MeSH
• genetická predispozice k nemoci genetika   MeSH
• hypertenze etiologie   genetika   patofyziologie   MeSH
• jednonukleotidový polymorfismus MeSH
• krevní tlak genetika   fyziologie   MeSH
• krysa rodu Rattus MeSH
• kuchyňská sůl škodlivé účinky   MeSH
• ledviny metabolismus   MeSH
• lokus kvantitativního znaku genetika   MeSH
• mapování chromozomů MeSH
• northern blotting MeSH
• polymerázová řetězová reakce s reverzní transkripcí MeSH
• potkani inbrední BN MeSH
• potkani inbrední SHR MeSH
• proteiny regulující apoptózu genetika   MeSH
• receptor melanokortinový typ 2 genetika   MeSH
• receptor melanokortinový typ 4 genetika   MeSH
• receptory melanokortinové genetika   MeSH
• savčí chromozomy genetika   MeSH
• sekvenční analýza hybridizací s uspořádaným souborem oligonukleotidů MeSH
• stanovení celkové genové exprese MeSH
• transplantace ledvin metody   MeSH
• tyrosinfosfatasa nereceptorového typu 2 genetika   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• Názvy látek
• CIDEA protein, rat MeSH Prohlížeč
• kuchyňská sůl MeSH
• melanocortin 5 receptor MeSH Prohlížeč
• proteiny regulující apoptózu MeSH
• Ptpn2 protein, rat MeSH Prohlížeč
• receptor melanokortinový typ 2 MeSH
• receptor melanokortinový typ 4 MeSH
• receptory melanokortinové MeSH
• tyrosinfosfatasa nereceptorového typu 2 MeSH