Hypertension in beta-adducin-deficient mice.
Polymorphic variants of the cytoskeletal protein adducin have been associated with hypertension in humans and rats. However, the direct role of this protein in modulating arterial blood pressure has never been demonstrated. To assess the effect of beta-adducin on blood pressure, a beta-adducin-deficient mouse strain (-/-) was studied and compared with wild-type controls (+/+). Aortic blood pressure was measured in nonanesthetized, freely moving animals with the use of telemetry implants. It is important to note that these mice have at least 98% of C57Bl/6 genetic background, with the only difference from wild-type animals being the beta-adducin mutation. We found statistically significant higher levels of systolic blood pressure (mm Hg) (mean+/-SE values: -/-: 126.94+/-1.14, n=5; +/+: 108.06+/-2. 34, n=6; P:</=0.0001), diastolic blood pressure (-/-: 83.54+/-1.07; +/+: 74.87+/-2.23; P:</=0.005), and pulse blood pressure (-/-: 43. 32+/-1.10; +/+: 33.19+/-1.96; P:</=0.001) in beta-adducin-deficient mice. Western blot analysis showed that as a result of the introduced genetic modification, beta-adducin was not present in heart protein extracts from -/- mice. Consequently, this deficiency produced a sharp decrease of alpha-adducin and a lesser reduction in gamma-adducin levels. However, we found neither cardiac remodeling nor modification of the heart function in these animals. This is the first report showing direct evidence that hypertension is triggered by a mutation in the adducin gene family.
Marro
M L
ML
International Center for Genetic Engineering and Biotechnology, Trieste, Italy.
Scremin
O U
OU
Jordan
M C
MC
Huynh
L
L
Porro
F
F
Roos
K P
KP
Gajovic
S
S
Baralle
F E
FE
Muro
A F
AF
D000818:Animals; D001794:Blood Pressure / Q000235:genetics; D002148:Calmodulin-Binding Proteins / Q000172:deficiency* / Q000235:genetics; D003598:Cytoskeletal Proteins / Q000172:deficiency* / Q000235:genetics; D004562:Electrocardiography; D006339:Heart Rate / Q000235:genetics / Q000502:physiology; D006352:Heart Ventricles / Q000473:pathology; D006973:Hypertension / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009206:Myocardium / Q000473:pathology; D000099291:Adducins
D002148:Calmodulin-Binding Proteins; D003598:Cytoskeletal Proteins; D000099291:Adducins