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1.
Eur J Immunogenet ; 30(4): 243-7, 2003 Aug.
Article de Anglais | MEDLINE | ID: mdl-12919284

RÉSUMÉ

Rat models are useful for the genetic dissection of the biology of innate immunity. Inbred rat strains were evaluated for carrageenan-induced innate inflammatory responses. Results indicated that the genetic control of innate immune responses is polygenic and influenced by gender, and may not necessarily be consistent with the genetics of experimental arthritis. The newly identified susceptible strains, in order of decreasing susceptibility, include Dahl salt-sensitive (S), Dahl salt-resistant (R), Milan normotensive strain (MNS) and Wistar Kyoto (WKY) rats. Similarly, the newly identified relatively resistant strains, in decreasing order of resistance, include DA rats, spontaneously hypertensive rats (SHRs) and Brown Norway (BN) rats. Linkage analyses using combinations of these susceptible and resistant strains are proposed.


Sujet(s)
Carragénane/métabolisme , Prédisposition génétique à une maladie , Immunité innée/immunologie , Inflammation/génétique , Inflammation/immunologie , Animaux , Croisements génétiques , Femelle , Inflammation/métabolisme , Mâle , Rats
2.
Hypertension ; 38(4): 779-85, 2001 Oct.
Article de Anglais | MEDLINE | ID: mdl-11641286

RÉSUMÉ

Aquantitative trait locus (QTL) for blood pressure was previously detected on rat chromosome 10 (RNO10) by linkage analysis and confirmed by the construction of congenic strains that encompass large regions of RNO10. In the present study, the rat RNO10 blood pressure QTL was dissected by the further construction of congenic substrains. The original congenic region was shown to contain 2 blood pressure QTLs (QTL 1 and QTL 2) approximately 24 cM apart. These were localized to a <2.6-cM region between markers D10Rat27 and D10Rat24 for QTL 1 and to a <3.2-cM region between D10Rat12 and D10Mco70 for QTL 2. Comparative mapping suggests that the rat RNO10 QTL 2 could be localized very close to a blood pressure QTL described by sib-pair analysis on human chromosome 17, but this is not definitively established because of multiple and complex chromosomal rearrangements between rodents and humans.


Sujet(s)
Pression sanguine/génétique , Chromosomes/génétique , Caractère quantitatif héréditaire , Animaux , Animaux congéniques , Poids/génétique , Femelle , Liaison génétique , Coeur/croissance et développement , Mâle , Taille d'organe/génétique , Rats , Rats de lignée Dahl , Rats de lignée LEW
3.
Genomics ; 72(1): 51-60, 2001 Feb 15.
Article de Anglais | MEDLINE | ID: mdl-11247666

RÉSUMÉ

It was previously shown using Dahl salt-sensitive (S) and salt-resistant (R) rats that a blood pressure quantitative trait locus (QTL) was present on rat chromosome 7. In the present work, this QTL was localized to a region less than 0.54 cM in size on the linkage map using a series of congenic strains. This region was contained in a single yeast artificial chromosome that was 220 kb long. This small segment still contained the primary candidate locus Cyp11b1 (11beta-hydroxylase), but the adjacent candidate genes Cyp11b2 (aldosterone synthase) and Cyp11b3 were ruled out. It is concluded that 11beta-hydroxylase, through its known genetic variants altering the production of 18-hydroxy-11-deoxy corticosterone, is very likely to account for the blood pressure QTL on chromosome 7 in the Dahl rat model of hypertension. This QTL accounts for about 23 mm Hg under the condition of 2% NaCl diet for 24 days.


Sujet(s)
Pression sanguine/génétique , Hypertension artérielle/génétique , Cartographie physique de chromosome , Caractère quantitatif héréditaire , Steroid 11-beta-hydroxylase/génétique , Allèles , Animaux , Animaux congéniques , Chromosomes artificiels de levure , Clonage moléculaire , Crossing-over , Cytochrome P-450 CYP11B2/génétique , Désoxycorticostérone/analogues et dérivés , Désoxycorticostérone/biosynthèse , Femelle , Coeur , Mâle , Répétitions microsatellites , Taille d'organe , Rats , Rats de lignée Dahl , Sodium alimentaire/administration et posologie , Sodium alimentaire/pharmacologie
4.
Physiol Genomics ; 4(3): 201-14, 2001 Jan 19.
Article de Anglais | MEDLINE | ID: mdl-11160999

RÉSUMÉ

A series of congenic strains were constructed in which segments of chromosome (chr) 1 from Lewis (LEW) rats were introgressed into the Dahl salt-sensitive (S) strain. Three blood pressure quantitative trait loci (QTL) were defined. Two of these (QTL 1a and QTL 1b) were closely linked in the region between 1q31 and 1q35. The third blood pressure QTL (QTL region 2) was close to the centromere between 1p11 and 1q12, which includes the candidate gene Slc9a3 for sodium/hydrogen exchange. The blood pressure QTL 1a and QTL 1b defined here overlap significantly with QTL for disease phenotypes of renal failure, stroke, ventricular mass, and salt susceptibility defined in other rat strains, implying that these disease phenotypes and our blood pressure phenotype have causes in common. QTL 1b also corresponded approximately with a blood pressure QTL described on human chr 15. The QTL region 2 corresponded approximately with blood pressure QTL described on mouse chr 10 and human chr 6.


Sujet(s)
Pression sanguine/génétique , Chromosomes/génétique , Caractère quantitatif héréditaire , Animaux , Animaux congéniques , Pression sanguine/physiologie , Poids/génétique , Poids/physiologie , Cartographie chromosomique , Marqueurs génétiques , Coeur/croissance et développement , Taille d'organe/génétique , Taille d'organe/physiologie , Rats , Rats de lignée Dahl , Rats de lignée LEW
5.
Physiol Genomics ; 3(1): 33-8, 2000 Jun 29.
Article de Anglais | MEDLINE | ID: mdl-11015598

RÉSUMÉ

Our purpose was to define quantitative trait loci (QTL) for blood pressure that differ between two widely used hypertensive rat strains, the Dahl salt-sensitive (S) rat and the spontaneously hypertensive rat (SHR). A genome scan was done on an F(2) (S x SHR) population fed 8% NaCl for 4 wk. Three blood pressure QTL were detected, one on each of rat chromosomes (chr) 3, 8, and 9. For the chr 3 QTL the SHR allele increased blood pressure, and for chr 8 and 9 the S allele increased blood pressure. The QTL on chr 9 was exceptionally strong, having a LOD score of 7.3 and accounting for 30% of the phenotypic variance and a difference of 40 mmHg between homozygotes. A review of the literature in conjunction with the present data suggests that S and SHR are not different for the previously described prominent blood pressure QTL on chr 1, 2, 10, and 13. QTL for body weight on chr 4, 12, 18, and 20, each with an effect of about 30 g, were incidentally observed.


Sujet(s)
Liaison génétique , Hypertension artérielle/génétique , Cartographie physique de chromosome , Caractère quantitatif héréditaire , Allèles , Animaux , Pression sanguine/effets des médicaments et des substances chimiques , Pression sanguine/génétique , Poids/génétique , Chromosomes/génétique , Croisements génétiques , Homozygote , Hypertension artérielle/induit chimiquement , Hypertension artérielle/métabolisme , Foie/métabolisme , Lod score , Mâle , Myocarde/métabolisme , Taille d'organe/génétique , Phénotype , Rats , Rats de lignée Dahl , Rats de lignée SHR , Chlorure de sodium/administration et posologie
6.
Physiol Genomics ; 1(3): 119-25, 1999 Nov 11.
Article de Anglais | MEDLINE | ID: mdl-11015570

RÉSUMÉ

We previously reported that markers on rat chromosome 1 are genetically linked to blood pressure in an F(2) population derived from Dahl salt hypertension-sensitive (S) and Lewis (LEW) rats. Because there was evidence for more than one blood pressure quantitative trait locus (QTL) on chromosome 1, an initial congenic strain introgressing a large 118-centimorgan (cM) segment of LEW chromosome 1 into the S background had been constructed. This initial congenic strain had a reduced blood pressure compared with S rats, proving the existence of a blood pressure QTL, but not giving a good localization of the QTL. In the present work a series of five overlapping congenic substrains were produced from the original congenic strain in order to localize a blood pressure QTL to a 25-cM region near the center of chromosome 1. The congenic substrains also ruled out the Sa locus as a blood pressure QTL in the S vs. LEW comparison because the Sa locus was contained in a congenic substrain that did not alter blood pressure.


Sujet(s)
Pression sanguine/génétique , Chromosomes/génétique , Caractère quantitatif héréditaire , Animaux , Animaux congéniques , Pression sanguine/physiologie , Technique de Northern , Poids , Cartographie chromosomique , Coenzyme A ligases , ADN/génétique , Femelle , Coeur/anatomie et histologie , Rein/métabolisme , Mâle , Répétitions microsatellites , Taille d'organe , Protéines/génétique , ARN messager/génétique , ARN messager/métabolisme , Rats , Rats de lignée Dahl , Rats de lignée LEW , Rats de lignée SHR , Rats de lignée WKY
7.
Genomics ; 51(2): 191-6, 1998 Jul 15.
Article de Anglais | MEDLINE | ID: mdl-9722941

RÉSUMÉ

A blood pressure quantitative trait locus was found (LOD = 5.0) on rat chromosome 9 using a large F2 population (N = 233) derived from Dahl salt-sensitive (S) and Dahl salt-resistant (R) rats. The F2 rats were fed 8% NaCl diet for 8 weeks. A congenic strain introgressing the R low-blood-pressure QTL allele on chromosome 9 into the S strain was constructed. The congenic strain, designated S.R(chr 9), had a lower blood pressure (19 mm Hg, P < 0.0001) and lower heart weight (112 mg, P < 0.0001) than S rats (2% NaCl diet for 24 days), proving the existence of a blood pressure QTL in the congenic region of about 21 cM.


Sujet(s)
Animaux congéniques , Pression sanguine/génétique , Cartographie chromosomique , Caractère quantitatif héréditaire , Rats de lignée Dahl , Animaux , Régime alimentaire , Génotype , Coeur , Croisement consanguin , Inhibines/génétique , Taille d'organe , Peptides/génétique , Rats , Chlorure de sodium alimentaire
8.
Genome Res ; 8(7): 711-23, 1998 Jul.
Article de Anglais | MEDLINE | ID: mdl-9685318

RÉSUMÉ

An F2 population (n = 151) derived from Dahl salt-sensitive (S) and Lewis rats was raised on a 8% NaCl diet for 9 weeks and analyzed for blood pressure quantitative trait loci (QTL) by use of a whole genome scan. Chromosomes 5 and 10 yielded lod scores for linkage to blood pressure that were significant; chromosomes 1, 2, 3, 8, 16, 17, and 18 gave lod scores suggestive for linkage. Chromosome 7 gave a significant signal for heart weight with a lesser effect on blood pressure. Congenic strains were constructed by introgressing Lewis low-blood-pressure QTL alleles for chromosomes 1, 5, 10, and 17 into the S genetic background. Congenic strains for chromosomes 1, 5, and 10 had significantly lower blood pressure than S, proving the existence of QTL on these chromosomes, but the chromosome 17 congenic strain failed to trap a contrasting QTL allele. The QTL allele increasing blood pressure originated from S rats for all QTL except those on chromosomes 2 and 7 in which the Lewis allele increased blood pressure. Interactions between each QTL and every other locus in the genome scan yielded significant interactions between chromosomes 10 and 4, and between chromosomes 2 and 3.


Sujet(s)
Génome , Hypertension artérielle/génétique , Caractère quantitatif héréditaire , Chlorure de sodium alimentaire/effets indésirables , Animaux , Animaux congéniques , Poids , Croisements génétiques , Liaison génétique , Génotype , Mâle , Phénotype , Rats , Rats de lignée BN , Rats de lignée LEW , Rats de lignée WKY
9.
Mamm Genome ; 9(7): 517-20, 1998 Jul.
Article de Anglais | MEDLINE | ID: mdl-9657847

RÉSUMÉ

Our purposes were to develop an improved linkage map for rat Chromosome 3 and to develop new markers polymorphic between Dahl salt-sensitive (S) and Dahl salt-resistant (R) rats. The linkage mapping panel consisted of three F2 populations totaling 359 rats. Twenty-five new markers were developed and placed on the linkage map. About half of these markers (13) were polymorphic between S and R rats. The final map spans 124.7 centiMorgans (cM) and includes 64 markers. The average distance between adjacent markers is 1.9 cM, and the largest separation is 10.5 cM.


Sujet(s)
Cartographie chromosomique , Rats/génétique , Animaux , Marqueurs génétiques , Répétitions microsatellites , Polymorphisme génétique , Lignées consanguines de rats
10.
J Clin Invest ; 101(8): 1591-5, 1998 Apr 15.
Article de Anglais | MEDLINE | ID: mdl-9541488

RÉSUMÉ

Previously we presented suggestive evidence from an F2 segregating population for an interaction on blood pressure (BP) between quantitative trait loci (QTL) on rat chromosomes (Chr) 2 and 10. To prove the existence of such an interaction, we developed congenic strains for Chr 2 and 10 by introgressing the low BP QTL alleles into the Dahl salt-sensitive (S) strain. A double congenic strain was also constructed with both the Chr 2 and 10 low BP QTL alleles on the S background. The four strains (S, Chr 2 congenic, Chr 10 congenic, and Chr 2/10 double congenic) were studied for BP response to increased salt intake. An analysis of variance showed significant main effects of Chr 2, Chr 10, and a significant interaction between Chr 2 and 10 on BP and heart weight (all P < 0.0001). The interaction accounted for 24 mmHg of BP and 79 mg of heart weight. Thus, the discovery and proof of epistatic interactions are clearly critical to understanding the genetics of blood pressure.


Sujet(s)
Pression sanguine/génétique , Épistasie , Allèles , Animaux , Cartographie chromosomique , Croisements génétiques , Femelle , Liaison génétique , Hypertension artérielle/génétique , Hypertension artérielle/anatomopathologie , Hypertension artérielle/physiopathologie , Mâle , Myocarde/anatomopathologie , Taille d'organe , Caractère quantitatif héréditaire , Rats , Lignées consanguines de rats , Rats de lignée WKY
11.
Mamm Genome ; 9(12): 1013-21, 1998 Dec.
Article de Anglais | MEDLINE | ID: mdl-9880670

RÉSUMÉ

In an effort to generate a genome-wide set of high-quality polymorphic markers for the rat, we used the marker-selection method, which has already been proven useful for the development of markers, especially for the human genome. Small-insert (300-900 bp) rat genomic libraries were constructed with an estimated complexity of three genome equivalents and enriched for short tandem repeat sequences (STRs). The enriched libraries were found to contain 45% (CA)n and 27% (GATA)n, representing at least a 50-fold enrichment over unselected small insert genomic libraries. A subset of 2160 STR-containing clones, primarily of the (GATA)n class of repeats, were sequenced. PCR primers flanking the repeats were synthesized from some of the sequences from the (CA)n and (GATA)n classes of STRs and tested for polymorphism in a panel of eight inbred rat strains. This strategy yielded 147 polymorphic markers, which mapped with high odds to all chromosomes by linkage in three F2 populations. The integration of these STR markers with other rat genetic markers and mapping reagents will facilitate the mapping of disease genes in the rat and the identification of loci associated with complex mammalian phenotypes.


Sujet(s)
Marqueurs génétiques/génétique , Génome , Banque génomique , Séquences répétées en tandem/génétique , Animaux , Séquence nucléotidique , Cartographie chromosomique , Chromosomes/génétique , Clonage moléculaire , ADN/composition chimique , ADN/génétique , Répétitions de dinucléotides/génétique , Répétitions microsatellites/génétique , Données de séquences moléculaires , Polymorphisme génétique , Rats , Rats de lignée BN , Rats de lignée LEW , Rats de lignée SHR , Rats de lignée WKY , Rat Sprague-Dawley
12.
Mamm Genome ; 8(12): 896-902, 1997 Dec.
Article de Anglais | MEDLINE | ID: mdl-9383281

RÉSUMÉ

11 beta-hydroxylase (Cyp11b1) mutations were previously linked to altered steroid biosynthesis and blood pressure in Dahl salt-resistant (R) and Dahl salt-sensitive (S) rats. In the present work, interval mapping identified a putative blood pressure quantitative trait locus (QTL) near Cyp11b1 in an F1(SxR)xS population (LOD = 2.0). Congenic rats (Designated S.R-Cyp11b) were constructed by introgressing the R-rat Cyp11b1 allele into the S strain. S.R-Cyp11b rats had significantly lower blood pressure and heart weight compared with S rats, proving the existence of a blood pressure QTL on Chromosome (Chr) 7 despite the fact that QTL linkage analysis of blood pressure never achieved stringent statistical criteria for significance. To test the effects of the introgressed region on blood pressure and survival, S.R.-Cyp11b and S rats were maintained on a 4% NaCl diet until they died or became moribund. Analysis of variance (ANOVA) indicated significant strain differences in blood pressure and days survived (P < 0.0001 for both) as well as gender differences in days survived (P = 0.0003). Kaplan-Meier survival analysis also found significant strain (P < 0.0001) and gender (P = 0.007) differences in days survived. However, when the effects of blood pressure were removed, significant strain differences in survival essentially disappeared. This suggests that the increased survival of S.R-Cyp11b rats was largely due to their decreased blood pressure and thus strongly corroborates the existence of a blood pressure QTL on Chr 7 near or at Cyp11b1.


Sujet(s)
Cartographie chromosomique , Hypertension artérielle/génétique , Caractère quantitatif héréditaire , Lignées consanguines de rats/génétique , Steroid 11-beta-hydroxylase/génétique , Hyperplasie congénitale des surrénales , Animaux , Pression sanguine , Croisements génétiques , Femelle , Hypertension artérielle/induit chimiquement , Tables de survie , Lod score , Longévité/génétique , Mâle , Myocarde/anatomopathologie , Taille d'organe , Rats , Facteurs sexuels , Chlorure de sodium alimentaire/toxicité
13.
Mamm Genome ; 8(9): 636-41, 1997 Sep.
Article de Anglais | MEDLINE | ID: mdl-9271663

RÉSUMÉ

The renin locus (Ren) on rat Chromosome (Chr) 13 had previously been shown to cosegregate with blood pressure in crosses involving Dahl salt-sensitive (S) and Dahl salt-resistant (R) rats. In the present work, interval mapping of blood pressure on Chr 13 with a large F2 (S x R), n = 233, population yielded a maximum LOD = 4.2 for linkage to blood pressure, but the quantitative trait locus (QTL) was only poorly localized to a large 35-centiMorgan (cM) segment of Chr 13. In the linkage analysis, the S-rat QTL allele (S) was associated with higher, and the R-rat QTL allele (R) with lower blood pressure, the difference between homozygotes being about 20 mm Hg. A congenic strain was made by introgressing the R-rat Ren allele into the recipient S strain. This congenic strain showed a 24 mm Hg reduction (P = 0.004) in blood pressure compared with S rats for rats fed 2% NaCl diet for 24 days; this difference was confirmed by two other independent tests. Two congenic substrains were derived from the first congenic strain with shorter R Chr 13 segments on the S background. Comparisons among these congenic strains showed that a blood pressure QTL was in the 24-cM chromosomal segment between Syt2 and D13M1Mit108. This segment does not include the renin locus, which is thus excluded from being the gene on rat Chr 13 responsible for genetic differences in blood pressure detected by linkage analysis.


Sujet(s)
Pression sanguine/génétique , Cartographie chromosomique , Lignées consanguines de rats/génétique , Chlorure de sodium alimentaire/pharmacologie , Animaux , Poids/génétique , Croisements génétiques , Résistance aux substances/génétique , Liaison génétique , Marqueurs génétiques , Génétique des populations , Haplotypes , Réaction de polymérisation en chaîne , Polymorphisme génétique , Rats , Rénine/génétique
14.
J Biol Chem ; 271(43): 26529-35, 1996 Oct 25.
Article de Anglais | MEDLINE | ID: mdl-8900122

RÉSUMÉ

Oligonucleotide site-directed mutations were introduced into the pelC gene of Erwinia chrysanthemi EC16 that directed single or double amino acid changes affecting disulfide linkages, calcium binding, catalysis, and protein folding. Subsequent characterization of the purified PelC mutant proteins demonstrated that pectinolytic function involves amino acids located near the calcium binding site rather than those surrounding an invariant vWiDH sequence. Wild-type PelC and the tested mutant proteins generally macerated plant tissue in proportion to their specific pectinolytic activity in vitro. However, some mutants gave higher maceration activity in plant tissue and elicited greater production of the phytoalexin, glyceollin, in soybean cotyledons than predicted by their in vitro pectinolytic activity. Most notable in this regard were three different mutations at lysine 172 with greatly reduced pectinolytic activity but as much elicitor activity as the wild-type protein. PelE macerated plant tissue 10 times more efficiently than PelC, as observed previously, but surprisingly showed equal activity in the elicitor assay. The results indicate that factors other than pectinolytic activity per se are involved in plant tissue maceration and elicitor activity.


Sujet(s)
Pectobacterium chrysanthemi/génétique , Isoenzymes/génétique , Isoenzymes/métabolisme , Mutagenèse dirigée , Plantes/métabolisme , Polysaccharide-lyases/génétique , Polysaccharide-lyases/métabolisme , Pectobacterium chrysanthemi/enzymologie , Hydrolyse , Pectine/métabolisme , Pliage des protéines
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