Portal de Periódicos da CAPES

Applicability of a “Speed” Congenic Strategy to Dissect Blood Pressure Quantitative Trait Loci on Rat Chromosome 2

2000; Lippincott Williams & Wilkins; Volume: 35; Issue: 1 Linguagem: Inglês

10.1161/01.hyp.35.1.179

1524-4563

Baxter Jeffs, Cervantes D. Negrín, Delyth Graham, James S. Clark, Niall Anderson, Dominique Gauguier, Anna F. Dominiczak,

Adipose Tissue and Metabolism

Abstract —The identification of any quantitative trait locus (QTL) via a genome scan is only the first step toward the ultimate goal of gene identification. The next step is the production of congenic strains by which the existence of a QTL may be verified and the implicated chromosomal region be reduced to a size applicable to positional cloning of the causal gene. We used a speed congenic breeding protocol previously verified in mice for 2 blood pressure QTLs on rat chromosome 2. Four congenic strains were produced through introgression of various segments of chromosome 2 from Wistar-Kyoto rats from Glasgow colonies [WKY (Gla) rats] into the recipient stroke-prone spontaneously hypertensive rats from Glasgow colonies [SHRSP (Gla) ], and vice versa. The number of backcross generations required for each strain to achieve complete homozygosity at 83 background genetic markers in a “best” male varied between 3 and 4. Transfer of the region of rat chromosome 2 containing both QTLs from WKY (Gla) into an SHRSP (Gla) genetic background lowered both baseline and salt-loaded systolic blood pressure by ≈20 and ≈40 mm Hg in male congenic rats compared with the SHRSP parental strain ( F =53.4, P <0.005; F =28.0, P < 0.0005, respectively). In contrast, control animals for stowaway heterozygosity presented no deviation from the blood pressure values recorded for the SHRSP (Gla) , indicating that if such heterozygosity exists, its effect on blood pressure is negligible. A reciprocal strategy in which 1 or both QTLs on rat chromosome 2 were transferred from SHRSP (Gla) into a WKY (Gla) genetic background resulted in statistically significant but smaller blood pressure increases for 1 of these QTLs. These results confirm the existence of blood pressure QTLs on rat chromosome 2 and demonstrate the applicability of a speed congenic strategy in the rat and emphasize the important role of the genetic background.