Genetic Isolation of Quantitative Trait Loci for Blood
Pressure Development and Renal Mass on Chromosome 5 in the
Spontaneously Hypertensive Rat
M. PRAVENEC1,2,
V. KŘEN1,2, D. KŘENOVÁ2, V. ZÍDEK1,
M. ŠIMÁKOVÁ1,
A. MUSILOVÁ1, J. VORLÍČEK1, E. ST.
LEZIN3, T. W. KURTZ3
1Institute of Physiology, Czech Academy of
Sciences, and Centre for Integrated Genomics, 2Institute
of Biology and Medical Genetics, First Faculty of Medicine,
Charles University, Prague, Czech Republic, 3Department
of Laboratory Medicine, University of California, San
Francisco, U.S.A.
Received February 6, 2002
Accepted July 11, 2002
Summary
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.
Key
words
SHR • Congenic strain • Chromosome 5 • Blood pressure • Renal
mass
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Michal Pravenec, Ph.D., Institute of Physiology, Czech Academy
of Sciences, Vídeňská 1083, 142 20 Prague 4, Czech Republic,
Phone/Fax: +420 24106 2297, e-mail:
pravenec@biomed.cas.cz
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