Effect of Add1 gene transfer on blood pressure in reciprocal congenic strains of Milan rats

Genetic variants of α adducin (ADD1) taken alone or in interaction with those of β (ADD2) and γ (ADD3) subunits have been associated with primary hypertension in humans and in Milan hypertensive (MHS) rats. In this study, we report the dissection of the individual contribution of each rat Add gene t...

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Bibliographic Details
Published in:Biochemical and biophysical research communications 2004-11, Vol.324 (2), p.562-568
Main Authors: Tripodi, Grazia, Florio, Monica, Ferrandi, Mara, Modica, Rossana, Zimdahl, Heike, Hubner, Norbert, Ferrari, Patrizia, Bianchi, Giuseppe
Format: Article
Language:English
Subjects:
Adducin
Animals
Animals, Congenic
Blood Pressure
Calmodulin-Binding Proteins - genetics
Calmodulin-Binding Proteins - metabolism
CCAAT-Enhancer-Binding Proteins - genetics
Chromosome Mapping
Chromosomes - ultrastructure
Congenic strains
Crosses, Genetic
DNA - metabolism
DNA-Binding Proteins - genetics
Female
Gene Transfer Techniques
Genetic Linkage
Genetics
Humans
Hypertension
Hypertension - genetics
Hypertension - pathology
Inbred MHS
Male
Models, Genetic
Rats
Sterol Regulatory Element Binding Protein 1
Transcription Factors - genetics
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Summary:Genetic variants of α adducin (ADD1) taken alone or in interaction with those of β (ADD2) and γ (ADD3) subunits have been associated with primary hypertension in humans and in Milan hypertensive (MHS) rats. In this study, we report the dissection of the individual contribution of each rat Add gene to blood pressure, by congenic substitution mapping. Congenic strains were developed by introgressing Add1, Add2, and Add3 genes (and chr14, chr4, and chr1 associated segments) of MHS in the Milan normotensive rat (MNS) genetic background (MNS.H-Add1, MNS.H-Add2, and MNS.H-Add3) and vice versa (MHS.N-Add1, MHS.N-Add2, and MHS.N-Add3). Systolic blood pressure (SBP) of MNS.H-Add1 rats was significantly higher (+10mmHg) than that of MNS, whereas SBP of MHS.N-Add1 was significantly lower (−10mmHg) than that of MHS. The differences account for 43% of the blood pressure differences between MHS and MNS. In contrast, SBPs of Add2 and Add3 congenic strains were not different from those of the correspondent recipient parental strain. The fine mapping of chr14 congenic segment supports the identity of blood pressure QTL with Add1 gene.
ISSN:0006-291X
1090-2104
DOI:10.1016/j.bbrc.2004.09.079