PMID- 15474463 OWN - NLM STAT- MEDLINE DCOM- 20041220 LR - 20101118 IS - 0006-291X (Print) IS - 0006-291X (Linking) VI - 324 IP - 2 DP - 2004 Nov 12 TI - Effect of Add1 gene transfer on blood pressure in reciprocal congenic strains of Milan rats. PG - 562-8 AB - Genetic variants of alpha adducin (ADD1) taken alone or in interaction with those of beta (ADD2) and gamma (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 (+10 mmHg) than that of MNS, whereas SBP of MHS.N-Add1 was significantly lower (-10 mmHg) 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. FAU - Tripodi, Grazia AU - Tripodi G AD - Prassis-Sigma Tau Research Institute, Settimo Milanese, Milan, Italy. grazia.tripodi@prassis.it FAU - Florio, Monica AU - Florio M FAU - Ferrandi, Mara AU - Ferrandi M FAU - Modica, Rossana AU - Modica R FAU - Zimdahl, Heike AU - Zimdahl H FAU - Hubner, Norbert AU - Hubner N FAU - Ferrari, Patrizia AU - Ferrari P FAU - Bianchi, Giuseppe AU - Bianchi G LA - eng PT - Journal Article PL - United States TA - Biochem Biophys Res Commun JT - Biochemical and biophysical research communications JID - 0372516 RN - 0 (ADD3 protein, human) RN - 0 (CCAAT-Enhancer-Binding Proteins) RN - 0 (Calmodulin-Binding Proteins) RN - 0 (DNA-Binding Proteins) RN - 0 (SREBF1 protein, human) RN - 0 (Srebf1 protein, rat) RN - 0 (Sterol Regulatory Element Binding Protein 1) RN - 0 (Transcription Factors) RN - 0 (adducin) RN - 9007-49-2 (DNA) SB - IM MH - Animals MH - Animals, Congenic MH - Blood Pressure MH - CCAAT-Enhancer-Binding Proteins/*genetics MH - Calmodulin-Binding Proteins/*genetics/metabolism MH - Chromosome Mapping MH - Chromosomes/ultrastructure MH - Crosses, Genetic MH - DNA/metabolism MH - DNA-Binding Proteins/*genetics MH - Female MH - *Gene Transfer Techniques MH - Genetic Linkage MH - Humans MH - Hypertension/genetics/pathology MH - Male MH - Models, Genetic MH - Rats MH - Sterol Regulatory Element Binding Protein 1 MH - Transcription Factors/*genetics EDAT- 2004/10/12 09:00 MHDA- 2004/12/21 09:00 CRDT- 2004/10/12 09:00 PHST- 2004/09/09 00:00 [received] PHST- 2004/10/12 09:00 [pubmed] PHST- 2004/12/21 09:00 [medline] PHST- 2004/10/12 09:00 [entrez] AID - S0006-291X(04)02140-0 [pii] AID - 10.1016/j.bbrc.2004.09.079 [doi] PST - ppublish SO - Biochem Biophys Res Commun. 2004 Nov 12;324(2):562-8. doi: 10.1016/j.bbrc.2004.09.079.