Which Sry locus is the hypertensive Y chromosome locus?

Area of Science:

• Genetics
• Cardiovascular Physiology
• Molecular Biology

Background:

• The Y chromosome in spontaneously hypertensive rats (SHR) carries a genetic factor elevating blood pressure compared to Wistar-Kyoto (WKY) rats.
• Previous research indicates a potential role for the Sry gene complex in this Y chromosome-mediated hypertension.

Purpose of the Study:

• To investigate the Sry gene complex as the hypertensive component of the SHR Y chromosome.
• To compare Sry loci sequences and expression patterns between hypertensive and normotensive rat strains.

Main Methods:

• Sequencing of Sry loci in SHR/Akr (hypertensive Y), SHR/Crl (normotensive Y), and WKY/Akr (normotensive Y) rat strains.
• Analysis of Sry locus copy number and sequence identity across strains.
• Quantification of total Sry gene expression in kidney and adrenal glands of SHR/y rats.

Main Results:

• SHR strains possess 7 Sry loci, while WKY rats have 6. A unique Sry3 locus exists in SHR strains but not WKY rats.
• The Sry3 locus sequence differs between SHR/Akr and SHR/Crl rats, with six accumulated mutations.
• Total Sry expression significantly increased in the SHR/y rat kidney from 4 to 15 weeks; kidney expression was markedly higher than in adrenal glands, with no significant inter-strain differences.

Conclusions:

• The presence of an SHR-specific Sry3 locus, its sequence divergence between SHR strains, and its expression pattern support its role as the Y chromosome-linked hypertensive component.
• The Sry gene complex is implicated as the genetic factor responsible for elevated blood pressure on the SHR Y chromosome.