Genetic analysis of alpha2-adrenergic receptors and blood pressure using Dahl salt-sensitive rats
OBJECTIVETo evaluate the role of α2-adrenergic receptors in genetic hypertension by cosegregation analysis using Dahl rats DESIGNInbred Dahl salt-sensitive (SS/Jr) rats were crossed with inbred Dahl salt-resistant (SR/Jr) rats; also, SS/Jr rats were crossed with several control strains, and large F2...
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| Veröffentlicht in: | Journal of hypertension 1994-04, Vol.12 (4), p.357-366 |
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| creator | Ginn, Dwight I Baptista, Carlos A.C Alam, Kiswar Y Deng, Alan Y Dene, Howard Le, Ha Kurtz, Theodore W Rapp, John P |
| description | OBJECTIVETo evaluate the role of α2-adrenergic receptors in genetic hypertension by cosegregation analysis using Dahl rats
DESIGNInbred Dahl salt-sensitive (SS/Jr) rats were crossed with inbred Dahl salt-resistant (SR/Jr) rats; also, SS/Jr rats were crossed with several control strains, and large F2 populations were subsequently produced from each cross. All F2 populations were raised on a high-salt diet. The rats were genotyped, where possible, at the loci for three different subtypes of α2-adrenergic receptors designated as classes I, II and III. The blood pressures of the rats classified by genotype at each α2-adrenergic receptor subtype locus were compared using analysis of variance
METHODSGenomic clones of three classes of α2-adrenergic receptors were isolated from genomic γ-phage libraries of SS/Jr or SR/Jr rat strains, or both, by screening with complementary DNA for human α2-adrenergic receptors. Fragments of the rat genomic clones obtained were used for genotyping by restriction fragment length polymorphism. Also, cloned genomic DNA flanking the α2-adrenergic receptors and containing microsatellites was sequenced; genotyping at informative microsatellite markers was performed using the polymerase chain reaction. Two of the three classes of rat α2-adrenergic receptors were localized to rat chromosomes by linkage analysis or using a panel of mouse-rat hybrid somatic cell lines
RESULTSRat α2-adrenergic receptor classes I and III genes were assigned to rat chromosomes 14 and 3, respectively. These correspond to α2-adrenergic receptor genes on human chromosomes 4 and 2, respectively. Extensive cosegregation analysis, involving five alleles in six segregating populations for class I α2-adrenergic receptors, yielded no evidence of an effect of these loci on blood pressure. Classes II and III α2-adrenergic receptors could each be tested in only one population and there was no evidence for an effect of either receptor gene on genetic differences in blood pressure. The dopamine-IB receptor was closely linked to the class I α2-adrenergic receptor on rat chromosome 14. Thus, the negative cosegregation of the class I receptor with blood pressure applies equally to the dopamine-1 B receptor
CONCLUSIONSGenetic analysis in segregating populations involving crosses of inbred Dahl salt-sensitive rats with five other strains provides no evidence for a genetic effect of class I α2-adrenergic receptors, or of the dopamine-1 B receptor, on blood pressure. Classes II an |
| doi_str_mv | 10.1097/00004872-199404000-00005 |
| format | Article |
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DESIGNInbred Dahl salt-sensitive (SS/Jr) rats were crossed with inbred Dahl salt-resistant (SR/Jr) rats; also, SS/Jr rats were crossed with several control strains, and large F2 populations were subsequently produced from each cross. All F2 populations were raised on a high-salt diet. The rats were genotyped, where possible, at the loci for three different subtypes of α2-adrenergic receptors designated as classes I, II and III. The blood pressures of the rats classified by genotype at each α2-adrenergic receptor subtype locus were compared using analysis of variance
METHODSGenomic clones of three classes of α2-adrenergic receptors were isolated from genomic γ-phage libraries of SS/Jr or SR/Jr rat strains, or both, by screening with complementary DNA for human α2-adrenergic receptors. Fragments of the rat genomic clones obtained were used for genotyping by restriction fragment length polymorphism. Also, cloned genomic DNA flanking the α2-adrenergic receptors and containing microsatellites was sequenced; genotyping at informative microsatellite markers was performed using the polymerase chain reaction. Two of the three classes of rat α2-adrenergic receptors were localized to rat chromosomes by linkage analysis or using a panel of mouse-rat hybrid somatic cell lines
RESULTSRat α2-adrenergic receptor classes I and III genes were assigned to rat chromosomes 14 and 3, respectively. These correspond to α2-adrenergic receptor genes on human chromosomes 4 and 2, respectively. Extensive cosegregation analysis, involving five alleles in six segregating populations for class I α2-adrenergic receptors, yielded no evidence of an effect of these loci on blood pressure. Classes II and III α2-adrenergic receptors could each be tested in only one population and there was no evidence for an effect of either receptor gene on genetic differences in blood pressure. The dopamine-IB receptor was closely linked to the class I α2-adrenergic receptor on rat chromosome 14. Thus, the negative cosegregation of the class I receptor with blood pressure applies equally to the dopamine-1 B receptor
CONCLUSIONSGenetic analysis in segregating populations involving crosses of inbred Dahl salt-sensitive rats with five other strains provides no evidence for a genetic effect of class I α2-adrenergic receptors, or of the dopamine-1 B receptor, on blood pressure. Classes II and III α2-adrenergic receptors also failed to cosegregate with blood pressure but, because only limited testing was possible with the classes II and III receptors, this negative result is not definitive</description><identifier>ISSN: 0263-6352</identifier><identifier>EISSN: 1473-5598</identifier><identifier>DOI: 10.1097/00004872-199404000-00005</identifier><identifier>CODEN: JOHYD3</identifier><language>eng</language><publisher>Hagerstown, MD: Lippincott-Raven Publishers</publisher><subject>Arterial hypertension. Arterial hypotension ; Biological and medical sciences ; Blood and lymphatic vessels ; Cardiology. Vascular system ; Experimental diseases ; Medical sciences</subject><ispartof>Journal of hypertension, 1994-04, Vol.12 (4), p.357-366</ispartof><rights>Lippincott-Raven Publishers.</rights><rights>1994 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c2465-59d45c60a7a15ab1bbfd8780b1f38d450c9ef625afa373e686ecd39e186d98ea3</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=4068787$$DView record in Pascal Francis$$Hfree_for_read</backlink></links><search><creatorcontrib>Ginn, Dwight I</creatorcontrib><creatorcontrib>Baptista, Carlos A.C</creatorcontrib><creatorcontrib>Alam, Kiswar Y</creatorcontrib><creatorcontrib>Deng, Alan Y</creatorcontrib><creatorcontrib>Dene, Howard</creatorcontrib><creatorcontrib>Le, Ha</creatorcontrib><creatorcontrib>Kurtz, Theodore W</creatorcontrib><creatorcontrib>Rapp, John P</creatorcontrib><title>Genetic analysis of alpha2-adrenergic receptors and blood pressure using Dahl salt-sensitive rats</title><title>Journal of hypertension</title><description>OBJECTIVETo evaluate the role of α2-adrenergic receptors in genetic hypertension by cosegregation analysis using Dahl rats
DESIGNInbred Dahl salt-sensitive (SS/Jr) rats were crossed with inbred Dahl salt-resistant (SR/Jr) rats; also, SS/Jr rats were crossed with several control strains, and large F2 populations were subsequently produced from each cross. All F2 populations were raised on a high-salt diet. The rats were genotyped, where possible, at the loci for three different subtypes of α2-adrenergic receptors designated as classes I, II and III. The blood pressures of the rats classified by genotype at each α2-adrenergic receptor subtype locus were compared using analysis of variance
METHODSGenomic clones of three classes of α2-adrenergic receptors were isolated from genomic γ-phage libraries of SS/Jr or SR/Jr rat strains, or both, by screening with complementary DNA for human α2-adrenergic receptors. Fragments of the rat genomic clones obtained were used for genotyping by restriction fragment length polymorphism. Also, cloned genomic DNA flanking the α2-adrenergic receptors and containing microsatellites was sequenced; genotyping at informative microsatellite markers was performed using the polymerase chain reaction. Two of the three classes of rat α2-adrenergic receptors were localized to rat chromosomes by linkage analysis or using a panel of mouse-rat hybrid somatic cell lines
RESULTSRat α2-adrenergic receptor classes I and III genes were assigned to rat chromosomes 14 and 3, respectively. These correspond to α2-adrenergic receptor genes on human chromosomes 4 and 2, respectively. Extensive cosegregation analysis, involving five alleles in six segregating populations for class I α2-adrenergic receptors, yielded no evidence of an effect of these loci on blood pressure. Classes II and III α2-adrenergic receptors could each be tested in only one population and there was no evidence for an effect of either receptor gene on genetic differences in blood pressure. The dopamine-IB receptor was closely linked to the class I α2-adrenergic receptor on rat chromosome 14. Thus, the negative cosegregation of the class I receptor with blood pressure applies equally to the dopamine-1 B receptor
CONCLUSIONSGenetic analysis in segregating populations involving crosses of inbred Dahl salt-sensitive rats with five other strains provides no evidence for a genetic effect of class I α2-adrenergic receptors, or of the dopamine-1 B receptor, on blood pressure. Classes II and III α2-adrenergic receptors also failed to cosegregate with blood pressure but, because only limited testing was possible with the classes II and III receptors, this negative result is not definitive</description><subject>Arterial hypertension. Arterial hypotension</subject><subject>Biological and medical sciences</subject><subject>Blood and lymphatic vessels</subject><subject>Cardiology. Vascular system</subject><subject>Experimental diseases</subject><subject>Medical sciences</subject><issn>0263-6352</issn><issn>1473-5598</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1994</creationdate><recordtype>article</recordtype><recordid>eNp1UctOxDAMjBBILAv_kAPXQNI0aXJEy1NC4gLnyk3d3UJoq7gL4u8JLHDDF8ueGcseM8aVPFPSV-cyR-mqQijvS1nmSny1zB5bqLLSwhjv9tlCFlYLq01xyI6InjPD-UovGNzggHMfOAwQP6gnPnYc4rSBQkCbMpjWGU0YcJrHRJnX8iaOY8unhETbhHxL_bDml7CJnCDOgnCgfu7fkCeY6ZgddBAJT37ykj1dXz2ubsX9w83d6uJehKK0RhjfliZYCRUoA41qmq51lZON6rTLkAweO1sY6EBXGq2zGFrtUTnbeoegl8zt5oY0EiXs6in1r5A-aiXrL6vqX6vqP6u-WyZLT3fSCShA7BIMoac_fSlt3qTKtHJHex_jjIle4vYdU73BfPSm_u8R-hO_U3oz</recordid><startdate>199404</startdate><enddate>199404</enddate><creator>Ginn, Dwight I</creator><creator>Baptista, Carlos A.C</creator><creator>Alam, Kiswar Y</creator><creator>Deng, Alan Y</creator><creator>Dene, Howard</creator><creator>Le, Ha</creator><creator>Kurtz, Theodore W</creator><creator>Rapp, John P</creator><general>Lippincott-Raven Publishers</general><general>Lippincott Williams & Wilkins</general><scope>IQODW</scope><scope>AAYXX</scope><scope>CITATION</scope></search><sort><creationdate>199404</creationdate><title>Genetic analysis of alpha2-adrenergic receptors and blood pressure using Dahl salt-sensitive rats</title><author>Ginn, Dwight I ; Baptista, Carlos A.C ; Alam, Kiswar Y ; Deng, Alan Y ; Dene, Howard ; Le, Ha ; Kurtz, Theodore W ; Rapp, John P</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c2465-59d45c60a7a15ab1bbfd8780b1f38d450c9ef625afa373e686ecd39e186d98ea3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1994</creationdate><topic>Arterial hypertension. Arterial hypotension</topic><topic>Biological and medical sciences</topic><topic>Blood and lymphatic vessels</topic><topic>Cardiology. Vascular system</topic><topic>Experimental diseases</topic><topic>Medical sciences</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ginn, Dwight I</creatorcontrib><creatorcontrib>Baptista, Carlos A.C</creatorcontrib><creatorcontrib>Alam, Kiswar Y</creatorcontrib><creatorcontrib>Deng, Alan Y</creatorcontrib><creatorcontrib>Dene, Howard</creatorcontrib><creatorcontrib>Le, Ha</creatorcontrib><creatorcontrib>Kurtz, Theodore W</creatorcontrib><creatorcontrib>Rapp, John P</creatorcontrib><collection>Pascal-Francis</collection><collection>CrossRef</collection><jtitle>Journal of hypertension</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ginn, Dwight I</au><au>Baptista, Carlos A.C</au><au>Alam, Kiswar Y</au><au>Deng, Alan Y</au><au>Dene, Howard</au><au>Le, Ha</au><au>Kurtz, Theodore W</au><au>Rapp, John P</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Genetic analysis of alpha2-adrenergic receptors and blood pressure using Dahl salt-sensitive rats</atitle><jtitle>Journal of hypertension</jtitle><date>1994-04</date><risdate>1994</risdate><volume>12</volume><issue>4</issue><spage>357</spage><epage>366</epage><pages>357-366</pages><issn>0263-6352</issn><eissn>1473-5598</eissn><coden>JOHYD3</coden><abstract>OBJECTIVETo evaluate the role of α2-adrenergic receptors in genetic hypertension by cosegregation analysis using Dahl rats
DESIGNInbred Dahl salt-sensitive (SS/Jr) rats were crossed with inbred Dahl salt-resistant (SR/Jr) rats; also, SS/Jr rats were crossed with several control strains, and large F2 populations were subsequently produced from each cross. All F2 populations were raised on a high-salt diet. The rats were genotyped, where possible, at the loci for three different subtypes of α2-adrenergic receptors designated as classes I, II and III. The blood pressures of the rats classified by genotype at each α2-adrenergic receptor subtype locus were compared using analysis of variance
METHODSGenomic clones of three classes of α2-adrenergic receptors were isolated from genomic γ-phage libraries of SS/Jr or SR/Jr rat strains, or both, by screening with complementary DNA for human α2-adrenergic receptors. Fragments of the rat genomic clones obtained were used for genotyping by restriction fragment length polymorphism. Also, cloned genomic DNA flanking the α2-adrenergic receptors and containing microsatellites was sequenced; genotyping at informative microsatellite markers was performed using the polymerase chain reaction. Two of the three classes of rat α2-adrenergic receptors were localized to rat chromosomes by linkage analysis or using a panel of mouse-rat hybrid somatic cell lines
RESULTSRat α2-adrenergic receptor classes I and III genes were assigned to rat chromosomes 14 and 3, respectively. These correspond to α2-adrenergic receptor genes on human chromosomes 4 and 2, respectively. Extensive cosegregation analysis, involving five alleles in six segregating populations for class I α2-adrenergic receptors, yielded no evidence of an effect of these loci on blood pressure. Classes II and III α2-adrenergic receptors could each be tested in only one population and there was no evidence for an effect of either receptor gene on genetic differences in blood pressure. The dopamine-IB receptor was closely linked to the class I α2-adrenergic receptor on rat chromosome 14. Thus, the negative cosegregation of the class I receptor with blood pressure applies equally to the dopamine-1 B receptor
CONCLUSIONSGenetic analysis in segregating populations involving crosses of inbred Dahl salt-sensitive rats with five other strains provides no evidence for a genetic effect of class I α2-adrenergic receptors, or of the dopamine-1 B receptor, on blood pressure. Classes II and III α2-adrenergic receptors also failed to cosegregate with blood pressure but, because only limited testing was possible with the classes II and III receptors, this negative result is not definitive</abstract><cop>Hagerstown, MD</cop><pub>Lippincott-Raven Publishers</pub><doi>10.1097/00004872-199404000-00005</doi><tpages>10</tpages></addata></record> |
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| ispartof | Journal of hypertension, 1994-04, Vol.12 (4), p.357-366 |
| issn | 0263-6352 1473-5598 |
| language | eng |
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| source | Journals@Ovid Complete |
| subjects | Arterial hypertension. Arterial hypotension Biological and medical sciences Blood and lymphatic vessels Cardiology. Vascular system Experimental diseases Medical sciences |
| title | Genetic analysis of alpha2-adrenergic receptors and blood pressure using Dahl salt-sensitive rats |
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