It was recognized that recombinant inbred strains are a very powerful system for the study of the genetics of hypertension, linkage analysis and gene mapping. Such set of recombinant inbred strains has been developed in the cooperation of Prof V. Kren and Dr. M. Pravenec in Prague. These recombinant inbred strains were used to search for the genes of spontaneous hypertension and to test the phenotypic differences. It was found that 1) the major histocompatibility complex of the rats showed a significant association with blood pressure, 2) the restriction fragment length polymorphism in kallikrein gene family as well as renin gene cosegregated with blood pressure, 3) Na+ leak in red blood cells cosegregated with blood pressure, 4) the relative heart and kidney weights are not closely related to mean arterial pressure and 5) the platelet aggregation and blood pressure are independent traits. The results indicate the usefulness of recombinant inbred strains in the analysis of the relationship between phenotype and genotype.

• MeSH
• hypertenze genetika   MeSH
• inbrední kmeny potkanů * MeSH
• krysa rodu Rattus MeSH
• lidé MeSH
• modely genetické MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• lidé MeSH
• zvířata MeSH
• Publikační typ
• práce podpořená grantem MeSH
• úvodníky MeSH

• MeSH
• hypertenze MeSH
• inbrední kmeny zvířat genetika   MeSH
• rekombinace genetická MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• dopisy MeSH
• komentáře MeSH

Recombinant inbred (RI) strains (Prague HXB/BXH set) represent a unique model that allows for permanent summation of genetic and physiological information as well as the study of age-dependent changes in phenotypes and/or gene regulation. This study compared blood pressure (BP) measured in adult animals of RI strains by radiotelemetry with BP values obtained in conscious rats of comparable age subjected to short-term carotid catheterization or with those obtained by direct carotid puncture under ether anesthesia (almost 20 years ago). After radiotelemetry recording, the contribution of major vasoactive systems to BP maintenance was studied by consecutive inhibition of the renin-angiotensin system (RAS), sympathetic nervous system (SNS), and nitric oxide synthase. We found highly significant interrelationships among baseline BP values obtained by radiotelemetry, carotid catheterization, or carotid puncture. This indicates considerable stability of RI strains over the course of their long existence, and confirms the reliability of BP values used for genetic studies performed in the past. Subsequent analysis of vasoactive system participation revealed the importance of SNS for the maintenance of BP, as determined by either radiotelemetry or catheterization. The BP of catheterized rats also correlated closely with acute captopril-induced BP changes, but this was not the case for rats measured by radiotelemetry. NO-dependent vasodilatation matched the BP effects of SNS and RAS in both measuring conditions. Residual BP (recorded at sodium nitroprusside-induced dilatation of resistance vessels) was also responsible for a significant portion of the BP variation in RI strains. Our study confirms the validity of RI strains for the further genetic and physiological research of hypertension.

• MeSH
• antihypertenziva farmakologie   MeSH
• hypertenze farmakoterapie   genetika   patofyziologie   MeSH
• inbrední kmeny potkanů genetika   MeSH
• katetrizace MeSH
• krevní tlak genetika   MeSH
• krysa rodu Rattus MeSH
• modely nemocí na zvířatech * MeSH
• monitorování fyziologických funkcí MeSH
• potkani inbrední SHR genetika   MeSH
• rekombinantní proteiny genetika   MeSH
• renin-angiotensin systém fyziologie   MeSH
• srdeční frekvence genetika   MeSH
• sympatický nervový systém fyziologie   MeSH
• synthasa oxidu dusnatého metabolismus   MeSH
• telemetrie MeSH
• velikost orgánu genetika   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• antihypertenziva MeSH
• rekombinantní proteiny MeSH
• synthasa oxidu dusnatého MeSH

We have constructed a genetic linkage map in the rat by analyzing the strain distribution patterns of 500 genetic markers in a large set of recombinant inbred strains derived from the spontaneously hypertensive rat and the Brown-Norway rat (HXB and BXH recombinant inbred strains). 454 of the markers could be assigned to specific chromosomes, and the amount of genome covered by the mapped markers was estimated to be 1151 centimorgans. By including a variety of morphologic, biochemical, immunogenetic, and molecular markers, the current map integrates and extends existing linkage data and should facilitate rat gene mapping and genetic studies of hypertension and other complex phenotypes of interest in the HXB and BXH recombinant inbred strains.

• MeSH
• DNA primery MeSH
• inbrední kmeny potkanů genetika   MeSH
• křížení genetické MeSH
• krysa rodu Rattus MeSH
• mapování chromozomů * MeSH
• molekulární sekvence - údaje MeSH
• myši MeSH
• potkani inbrední BN MeSH
• potkani inbrední SHR MeSH
• rekombinace genetická MeSH
• sekvence nukleotidů MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• DNA primery MeSH

1. The HXB/BXH recombinant inbred (RI) strains, derived from the spontaneously hypertensive rat (SHR) and the normotensive Brown Norway (BN.1x) rat, represent a very useful system for gene mapping and for genetic analysis of certain model diseases, such as spontaneous hypertension. 2. These RI strains were genotyped in multiple genetic polymorphisms and characterized in blood pressure and some intermediate phenotypes. 3. The analysis of RI strains has revealed that (i) a gene in the vicinity of the major histocompatibility complex (RT1) on chromosome 20, a kallikrein-related gene on chromosome 4 and the renin gene on chromosome 13 were significantly associated with blood pressure, and (ii) Na+ leak in red blood cells correlated with blood pressure whereas relative heart and kidney weights as well as platelet aggregation did not.

• MeSH
• fenotyp * MeSH
• hypertenze genetika   MeSH
• krysa rodu Rattus MeSH
• modely nemocí na zvířatech MeSH
• potkani inbrední BN genetika   MeSH
• potkani inbrední SHR genetika   MeSH
• rekombinace genetická * MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

• MeSH
• DNA chemie   MeSH
• druhová specificita MeSH
• genetické markery MeSH
• genom MeSH
• inbrední kmeny potkanů genetika   MeSH
• krysa rodu Rattus MeSH
• mapování chromozomů * MeSH
• polydaktylie genetika   MeSH
• polymorfismus genetický MeSH
• potkani inbrední BN MeSH
• potkani inbrední SHR MeSH
• rekombinace genetická MeSH
• syndrom MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• DNA MeSH
• genetické markery MeSH

Heart and kidney weight of newborn rats was studied in two progenitor strains (Brown Norway-BN, and spontaneously hypertensive rats-SHR) and in 31 recombinant inbred (RI) strains developed by inbreeding of F2 cross derived from these two progenitors. The relative weight of both organs was significantly higher in SHR newborns than in BN ones. No differences in relative DNA, protein and water contents were detected in hearts from SHR and BN newborns. On the other hand, in SHR kidneys there was lower DNA and protein content accompanied by a higher water content. This suggested that kidneys of SHR babies had less cells with higher water content. The average body weight of newborns in individual RI strains was continuously distributed between both progenitor strains but more RI strains resembled values of SHR newborns. The opposite was true for relative heart and kidney weights where the predominant influence of BN genes was visible. Moreover, there was an important difference between two reciprocal crosses of RI strains because the relative heart weight was clustered around SHR values only in BxH but not in HxB cross. This was, however, not observed for body weight and relative kidney weight. No significant correlation between blood pressure of adult males and body weight or relative organ weights of newborns of RI strains was found. On the other hand, relative heart and kidney weights of newborns correlated positively with the same parameters in adult males of respective RI strains. Additionally, relative heart weight of newborns was related positively to blood pressure of their mothers only in HxB cross that was derived from SHR females. It can be concluded that 1) kidney enlargement observed in newborn SHR is due to increased water content, 2) organ weight in adulthood can be predicted from newborn organ weight, and 3) heart weight in newborns correlated significantly with maternal blood pressure in HxB but not in BxH cross. It should be noted that the relationship between heart and/or kidney weight at birth and blood pressure in adulthood has not been proven to be significant (at p < 0.05 level) in Prague set of recombinant inbred strains.

• MeSH
• diastola MeSH
• DNA metabolismus   MeSH
• hypertenze patologie   patofyziologie   MeSH
• krevní tlak MeSH
• krysa rodu Rattus MeSH
• ledviny patologie   MeSH
• myokard metabolismus   patologie   MeSH
• novorozená zvířata anatomie a histologie   metabolismus   MeSH
• pohlavní dimorfismus MeSH
• potkani inbrední BN MeSH
• potkani inbrední SHR MeSH
• referenční hodnoty MeSH
• rekombinace genetická MeSH
• stárnutí fyziologie   MeSH
• velikost orgánu MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• DNA MeSH

The teratogenic effect of all-trans retinoic acid (RA) was tested in the system of congenic and recombinant inbred (RI) strains of the laboratory rat carrying the mutant Lx allele which determines the polydactyly-luxate syndrome. It was demonstrated that the teratogenic effect of RA is influenced by both the genotype at the Lx locus and the modifying genes. The dose of 100 mg/kg administered by gavage on day 11 of pregnancy induced a statistically significant incidence of preaxial polydactyly in hind limbs of LEW/BN, +/Lx foetuses heterozygous in the mutant allele, whereas no specific limb defects were noted in foetuses LEW/BN, +/+ without the mutant allele. In foetuses homozygous in the mutant allele LEW/BN, Lx/Lx and SHR/BXH2, Lx/Lx, RA conversely induced a significant reduction in the number of toes on the preaxial side of hind limbs and a reduction of the zeugopodium, mostly the tibia. Reduction changes were more marked in SHR/BXH2, Lx/Lx foetuses, in which the tibia was entirely missing and sirenomelia was found. The foetuses in this group have in their genetic background a combination of modifiers that are responsible for oligodactyly and tibial hemimelia in the BXH2 strain. On the basis of continuing mapping of the rat genome, the testing of RA in the system of RI and congenic strains will be utilized for identification of so far hypothetical genes involved in morphogenesis.

• MeSH
• genotyp MeSH
• inbreeding MeSH
• končetiny patologie   MeSH
• krysa rodu Rattus MeSH
• polydaktylie genetika   MeSH
• potkani inbrední BN MeSH
• potkani inbrední LEW MeSH
• potkani inbrední SHR MeSH
• rekombinace genetická * MeSH
• teratogeny farmakologie   MeSH
• tretinoin farmakologie   MeSH
• zadní končetina účinky léků   patologie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• teratogeny MeSH
• tretinoin MeSH

The mode of blood pressure inheritance and some genetic markers of spontaneous hypertension were evaluated in a new set of recombinant inbred (RI) strains obtained by crossing of normotensive (BN.lx) and hypertensive (SHR) progenitor strains. Blood pressure values of RI strains were continuously distributed between both progenitor strains, although normotensive strains slightly prevailed. Statistical analysis suggested that there are three major genes and multiple minor genes responsible of the determination of spontaneous hypertension. The association between blood pressure and gene(s) within RT1 complex or gene(s) closely linked to it was found by RI strain analysis. This suggestion was confirmed by the detection of significant difference in blood pressure between SHR and SHR.1N congenic strains. Our results indicate that RT1 complex gene(s) may be involved in the development of high blood pressure.

• MeSH
• chov MeSH
• genetické markery MeSH
• hypertenze genetika   MeSH
• inbrední kmeny potkanů genetika   MeSH
• krevní tlak MeSH
• krysa rodu Rattus MeSH
• potkani inbrední SHR genetika   MeSH
• rekombinace genetická MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• genetické markery MeSH

Recombinant inbred (RI) and congenic strains carrying the polydactyly-luxate syndrome (PLS) provide an experimental model for the analysis of polygenic control of limb development. PLS is determined by a major gene Lx whose phenotypic expression is strongly influenced by the genetic background upon which it operates. The morphometric analysis of the skeleton of front and hind legs has been carried out. The morphotypes of PLS in RI strains exhibit a continuous variability and transgressive variation compared to BN.Lx and SHR.Lx morphotypes, which strongly indicates the polygenic effects on PLS manifestation. Quantitative trait loci (QTL) were searched for through correlation of genetic markers and morphometric traits. The association analysis revealed statistically significant correlations (P < 0.0003) of morphometric traits with two markers on chromosome 4 (Il6 and A2m) associated with the number of front feet and hind feet phalanges, respectively, one marker on chromosome 7 (D7Mit17) associated with the tibia length, and the somatostatin gene on chromosome 11 associated with the number of front feet phalanges. In addition, suggestive associations of morphometric traits with markers on further nine chromosomes have been found (correlation coefficients ranging from 0.5 to 0.6). The verification of all these findings is in progress by means of double congenic strains which, in addition to the Lx gene, carry differential chromosome segments with putative modifiers.

• MeSH
• genetické markery MeSH
• inbreeding MeSH
• končetiny patologie   MeSH
• krysa rodu Rattus MeSH
• morfogeneze MeSH
• polydaktylie genetika   MeSH
• potkani inbrední BN MeSH
• potkani inbrední SHR MeSH
• rekombinace genetická * MeSH
• zadní končetina patologie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• genetické markery MeSH