Genetic isolation of quantitative trait loci for blood pressure development and renal mass on chromosome 5 in the spontaneously hypertensive rat.
Total genome scans of genetically segregating populations derived from spontaneously hypertensive rats (SHR) and other rat models of essential hypertension suggested a presence of quantitative trait loci (QTL) regulating blood pressure on multiple chromosomes, including chromosome 5. The objective of the current study was to test directly a hypothesis that chromosome 5 of the SHR carries a blood pressure regulatory QTL. A new congenic strain was derived by replacing a segment of chromosome 5 in the SHR/Ola between the D5Wox20 and D5Rat63 markers with the corresponding chromosome segment from the normotensive Brown Norway (BN/Crl) rat. Arterial pressures were directly monitored in conscious, unrestrained rats by radiotelemetry. The transfer of a segment of chromosome 5 from the BN strain onto the SHR genetic background was associated with a significant decrease of systolic blood pressure, that was accompanied by amelioration of renal hypertrophy. The heart rates were not significantly different in the SHR compared to SHR chromosome 5 congenic strain. The findings of the current study demonstrate that gene(s) with major effects on blood pressure and renal mass exist in the differential segment of chromosome 5 trapped within the new SHR.BN congenic strain.
Pravenec
M
M
Institute of Physiology, Czech Academy of Sciences, Prague, Czech Republic. pravenec@biomed.cas.cz
Kren
V
V
Krenová
D
D
Zídek
V
V
Simáková
M
M
Musilová
A
A
Vorlícek
J
J
Lezin
E St
ES
Kurtz
T W
TW
D000704:Analysis of Variance; D000818:Animals; D020296:Animals, Congenic; D001794:Blood Pressure / Q000235:genetics / Q000502:physiology; D001835:Body Weight; D002874:Chromosome Mapping; D033481:Chromosomes, Mammalian / Q000235:genetics*; D003433:Crosses, Genetic; D005260:Female; D005838:Genotype; D006339:Heart Rate; D006973:Hypertension / Q000235:genetics* / Q000503:physiopathology; D006984:Hypertrophy / Q000473:pathology; D007668:Kidney / Q000473:pathology*; D008297:Male; D009929:Organ Size; D040641:Quantitative Trait Loci / Q000235:genetics*; D051381:Rats; D011914:Rats, Inbred BN; D011918:Rats, Inbred SHR; D013686:Telemetry / Q000379:methods; D013997:Time Factors