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Effect of renin gene transfer on blood pressure in the spontaneously hypertensive rat.

https://arctichealth.org/en/permalink/ahliterature52982
Source
Hypertension. 1998 Jan;31(1 Pt 2):373-7
Publication Type
Article
Date
Jan-1998
Author
E. St Lezin
W. Liu
N. Wang
J M Wang
V. Kren
V. Zidek
M. Zdobinska
D. Krenova
A. Bottger
B F van Zutphen
M. Pravenec
Author Affiliation
Department of Laboratory Medicine, University of California, San Francisco 94120, USA. stlezin@pangloss.ucsf.edu
Source
Hypertension. 1998 Jan;31(1 Pt 2):373-7
Date
Jan-1998
Language
English
Publication Type
Article
Keywords
Animals
Blood Pressure - genetics - physiology
Cholesterol - blood
Chromosome Mapping
Crosses, Genetic
Gene Transfer Techniques
Genetic markers
Genotype
Heart rate - genetics
Hypertension - blood - genetics
Lipoproteins - blood
Phenotype
Quantitative Trait, Heritable
Rats
Rats, Inbred BN
Rats, Inbred SHR
Renin - biosynthesis - genetics
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.
Triglycerides - blood
Abstract
To investigate whether molecular variation in the renin gene contributes to the greater blood pressure of spontaneously hypertensive rats (SHR) versus normotensive Brown Norway (BN) rats, we measured blood pressure in an SHR progenitor strain and an SHR congenic strain that are genetically identical except at the renin gene and an associated segment of chromosome 13 transferred from the BN strain. Backcross breeding and molecular selection at the renin locus were used to create the SHR congenic strain (designated SHR.BN-Ren) that carries the renin gene transferred from the normotensive BN strain. We found that transfer of the renin gene from the BN strain onto the genetic background of the SHR did not decrease blood pressure in rats fed either a normal or high-salt diet. In fact, the systolic blood pressures of the SHR congenic rats tended to be slightly greater than the systolic blood pressures of the SHR progenitor rats. However, the congenic strain exhibited lower serum high-density lipoprotein cholesterol, and greater levels of total cholesterol, very-low-density lipoprotein, and intermediate-density lipoprotein cholesterol during administration of a high-fat, high-cholesterol diet. These findings demonstrate that (1) under the environmental circumstances of the current study, the greater blood pressure of SHR versus BN rats cannot be explained by strain differences in the renin gene and (2) a quantitative trait locus affecting lipid metabolism exists on chromosome 13 within the transferred chromosome segment. The SHR.BN-Ren congenic strain may provide a useful new animal model for studying the interaction between high blood pressure and dyslipidemia in cardiovascular disease.
PubMed ID
9453331 View in PubMed
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Endotoxin response in spontaneously hypertensive rats: a role of the TNFalpha-gene region.

https://arctichealth.org/en/permalink/ahliterature57273
Source
Folia Biol (Praha). 1999;45(1):3-6
Publication Type
Article
Date
1999
Author
Z. Pausova
J. Kunes
V. Kren
D. Krenová
M. Pravenec
J. Tremblay
P. Hamet
Author Affiliation
Centre Hospitalier de l'Université de Montréal, Canada.
Source
Folia Biol (Praha). 1999;45(1):3-6
Date
1999
Language
English
Publication Type
Article
Keywords
Animals
Animals, Congenic
Chromosome Mapping
Comparative Study
Endotoxemia - complications - genetics - physiopathology
Fever - etiology - physiopathology
Gene Expression Regulation
Hypothermia - etiology - physiopathology
Rats
Rats, Inbred SHR - genetics
Research Support, Non-U.S. Gov't
Tumor Necrosis Factor-alpha - biosynthesis - genetics
Abstract
We have shown previously that administration of endotoxin induces a smaller decrease of body temperature in spontaneously hypertensive rats (SHR) than in normotensive Brown Norway (BN) rats. Several studies have suggested that tumor necrosis factor alpha (TNFalpha) is one of the mediators of the body-temperature response to endotoxin. To test whether the TNFalpha gene could be involved in determination of the observed difference in the body-temperature response to endotoxin, we studied SHR (n = 6) and a congenic strain, SHR.1N (n = 5), which differs from SHR by a segment of chromosome 20 originating from BN and containing the TNFalpha gene. Body temperature was recorded continuously by means of radiotelemetry. We showed that, in both strains, an intraperitoneal injection of endotoxin (500 microg/kg of body weight) induces a rapid hyperthermic phase (20-40 minutes post-injection), which is followed, first, by a hypothermic phase (100-120 minutes post-injection) and, then, by a late hyperthermic phase (seven hours). Although both strains demonstrated a similar trend in the response, a significant difference was observed between the two response curves (P = 0.0001). Further analysis at each time point revealed that the two strains differed significantly at a peak of the hypothermic phase (P = 0.035) and the late hyperthermic phase (P = 0.035). In conclusion, these data indicate that the differential chromosomal segment of SHR.1N contains a gene(s) causally related to the body-temperature response to endotoxin. In the light of previously published data, the TNFalpha gene appears to be the most likely candidate gene within the segment.
PubMed ID
10732711 View in PubMed
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Genetic analysis of anti-TBM disease in the Norway rat.

https://arctichealth.org/en/permalink/ahliterature57863
Source
Folia Biol (Praha). 1985;31(4):261-72
Publication Type
Article
Date
1985
Author
A. Panczak
V. Kren
J. Stejskal
D. Schlegerová
Source
Folia Biol (Praha). 1985;31(4):261-72
Date
1985
Language
English
Publication Type
Article
Keywords
Animals
Basement Membrane - immunology
Female
Genes, MHC Class II
Genotype
Heterozygote
Immunization
Kidney Diseases - genetics - immunology
Kidney Tubules - immunology
Linkage (Genetics)
Male
Rats
Rats, Inbred BN - genetics
Rats, Inbred Strains - genetics
Abstract
The anti-tubular basement membrane (TBM) disease was found in own kidneys of BN, but not BN.1B rats, after immunization with BP.1N (or BP) allogeneic kidney homogenate in CFA. Both humoral [anti-TBM reaction assessed by direct immunofluorescence (IF)] and cellular response to TBM antigen (tubulointerstitial nephritis and giant cell infiltration) appeared to be controlled by an MHC-linked Ir gene(s). In the present experiments all of the 54 RT1b/RT1n heterozygous Bc rats (BN.1B x BN) x BN.1B were found to be anti-TBM positive by direct IF following the immunization mentioned above, as were all (BN.1B x BN)F1 hybrids. Among 51 RT1b/RT1b Bc homozygotes, 5 animals formed linear anti-TBM deposition in their own kidneys. The direct IF staining was somewhat weaker than in the preceding groups but continuous. However, circulating anti-TBM antibodies were not proven by indirect IF in these rats. BN animals failed to develop anti-TBM disease not only after syngeneic immunization but also after BN.1B inoculum differing in RT1 antigens alone. Only donor-recipient strain combinations involving non-RT1 differences (BP or BP.1N to BN, BN.1B or BN to BP.1N) were susceptible to the anti-TBM response. Thus the previously revealed adjuvant effect of non-RT1 alloantigenic differences was confirmed, whereas RT1 difference had no such effect nor was involved in it. In conclusion, the main anti-TBM Ir gene seems to be closely linked with, or even included in, the RT1n haplotype in our system of congenic strains. An alternative hypothesis is that there may be two separately functioning Ir genes, one within the RT1n allele and the other in linkage with RT1.
PubMed ID
3930301 View in PubMed
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Genetic regulation of catecholamine synthesis, storage and secretion in the spontaneously hypertensive rat.

https://arctichealth.org/en/permalink/ahliterature97424
Source
Hum Mol Genet. 2010 Jul 1;19(13):2567-80
Publication Type
Article
Date
Jul-1-2010
Author
M L Jirout
R S Friese
N R Mahapatra
M. Mahata
L. Taupenot
S K Mahata
V. Kren
V. Zídek
J. Fischer
H. Maatz
M G Ziegler
M. Pravenec
N. Hubner
T J Aitman
N J Schork
D T O'Connor
Author Affiliation
Department of Medicine, University of California, San Diego, La Jolla, CA 92037, USA.
Source
Hum Mol Genet. 2010 Jul 1;19(13):2567-80
Date
Jul-1-2010
Language
English
Publication Type
Article
Abstract
Understanding catecholamine metabolism is crucial for elucidating the pathogenesis of hereditary hypertension. Here we integrated transcriptional and biochemical profiling with physiologic quantitative trait locus (eQTL and pQTL) mapping in adrenal glands of the HXB/BXH recombinant inbred (RI) strains, derived from the spontaneously hypertensive rat (SHR) and normotensive Brown Norway (BN.Lx). We found simultaneous down-regulation of five heritable transcripts in the catecholaminergic pathway in young (6 weeks) SHRs. We identified cis-acting eQTLs for Dbh, Pnmt (catecholamine biosynthesis) and Vamp1 (catecholamine secretion); enzymatic activities of Dbh and Pnmt paralleled transcripts, with pQTLs for activities mirroring eQTLs. We also detected trans-regulated expression of Vmat1 and Chga (both involved in catecholamine storage), with co-localization of these trans-eQTLs to the Pnmt locus. Pnmt re-sequencing revealed promoter polymorphisms that result in decreased response of the transfected SHR promoter to glucocorticoid, compared with BN.Lx. Of physiological pertinence, Dbh activity negatively correlated with systolic blood pressure in RI strains, whereas Pnmt activity was negatively correlated with heart rate. The finding of such cis- and trans-QTLs at an age before the onset of frank hypertension suggests that these heritable changes in biosynthetic enzyme expression represent primary genetic mechanisms for regulation of catecholamine action and blood pressure control in this widely studied model of hypertension.
PubMed ID
20378607 View in PubMed
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HSP27 locus cosegregates with left ventricular mass independently of blood pressure.

https://arctichealth.org/en/permalink/ahliterature54596
Source
Hypertension. 1996 Dec;28(6):1112-7
Publication Type
Article
Date
Dec-1996
Author
P. Hamet
M A Kaiser
Y. Sun
V. Pagé
M. Vincent
V. Kren
M. Pravenec
J. Kunes
J. Tremblay
N J Samani
Author Affiliation
Centre de Recherche Hôtel-Dieu de Montréal, Université de Montréal, Canada.
Source
Hypertension. 1996 Dec;28(6):1112-7
Date
Dec-1996
Language
English
Publication Type
Article
Keywords
Alleles
Animals
Autoradiography
Blood Pressure - genetics
Heat-Shock Proteins - genetics
Hypertrophy, Left Ventricular - genetics
Male
Polymerase Chain Reaction
Rats
Rats, Inbred SHR
Rats, Inbred WKY
Research Support, Non-U.S. Gov't
Abstract
Left ventricular hypertrophy remains a significant clinical problem and a predictor of fatal outcome in hypertension. Blood pressure per se and environmental modifiers including stress affect cardiac mass. Heat shock proteins are involved in the stress response as well as in the regulation of cardiac growth and cytoprotection. The present study evaluates heat shock protein 27 as a locus marker or candidate gene of cardiac hypertrophy in hypertension. The spontaneously hypertensive rat allele of heat shock protein 27 was associated with about a 6% increase in relative left ventricular weight (P = .0112) in 30 recombinant inbred strains from crosses of Brown Norway and spontaneously hypertensive rats. In 336 F2 crosses of spontaneously hypertensive and Wistar-Kyoto rats, the hypertensive allele was dominant and cosegregated with a similar 6% increase in the ratio of left ventricular weight to body weight (P = .0058) in rats fed a normal salt diet, but its contribution to left ventricular weight decreased in rats kept on a high salt diet. The contribution of the heat shock protein 27 allele was independent of blood pressure. We suggest that heat shock protein 27 represents a candidate gene/locus marker of cardiac hypertrophy in hypertension.
PubMed ID
8952607 View in PubMed
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Mapping of quantitative trait loci for seminal vesicle mass and litter size to rat chromosome 8.

https://arctichealth.org/en/permalink/ahliterature64007
Source
J Reprod Fertil. 1999 Jul;116(2):329-33
Publication Type
Article
Date
Jul-1999
Author
V. Zídek
J. Pintír
A. Musilová
V. Bílá
V. Kren
M. Pravenec
Author Affiliation
Institute of Physiology, Czech Academy of Sciences, Prague, Czech Republic.
Source
J Reprod Fertil. 1999 Jul;116(2):329-33
Date
Jul-1999
Language
English
Publication Type
Article
Keywords
Animals
Chromosome Mapping
Comparative Study
Genotype
Likelihood Functions
Litter Size - genetics
Male
Phenotype
Quantitative Trait, Heritable
Rats
Rats, Inbred BN - genetics
Rats, Inbred SHR - genetics
Recombination, Genetic
Regression Analysis
Research Support, Non-U.S. Gov't
Seminal Vesicles - anatomy & histology
Variation (Genetics)
Abstract
The spontaneously hypertensive rat (SHR) and the Brown Norway (BN) rat differ significantly in litter size (7.6 versus 4.5 pups). In the HXB and BXH sets of recombinant inbred (RI) strains derived from SHR and BN rats, heritability of litter size and of selected male reproductive parameters such as sperm production, sperm count, sperm morphology and motility, and the mass of the testis, epididymides, and seminal vesicles were estimated and a search was undertaken for quantitative trait loci (QTL) associated with these phenotypes. The mass of seminal vesicles was significantly associated with a QTL near the D8Cebr204S21 marker on chromosome 8 (LOD score = 4.1, P = 0.00001); this QTL was responsible for 46% of the genetic variability of the trait. The same gene marker on chromosome 8 also showed a suggestive association with the litter size. Litter size was significantly correlated with the mass of seminal vesicles (r = 0.58, P = 0.003). These findings indicate that the variability in litter size among RI strains may be due in part to differences in the mass of seminal vesicles and it is possible that both mass of seminal vesicles and litter size are determined by a pleiotropic effect of the same QTL on rat chromosome 8.
PubMed ID
10615258 View in PubMed
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MHC control of autoimmune anti-TBM reaction in the Norway rat.

https://arctichealth.org/en/permalink/ahliterature57887
Source
Folia Biol (Praha). 1983;29(5):337-48
Publication Type
Article
Date
1983
Author
A. Panczak
V. Kren
J. Stejskal
D. Schlegerová
Source
Folia Biol (Praha). 1983;29(5):337-48
Date
1983
Language
English
Publication Type
Article
Keywords
Animals
Autoantibodies - immunology
Basement Membrane - immunology
Genes, MHC Class II
Graft Rejection
Kidney - immunology
Kidney Tubules - immunology
Major Histocompatibility Complex
Microscopy, Electron
Rats
Rats, Inbred Strains
Abstract
The RT1 control of anti-TBM reaction presupposed in rat kidney transplantations has been revealed in immunization experiments performed in similar strain combinations. The anti-TBM reaction proven by immunofluorescence and in some cases even tubulointerstitial nephritis with giant cell infiltration developed in kidneys of BN rats immunized with BP.1N (or BP) kidney homogenate in CFA. On the contrary, BN.1B recipients of BP (or BP.1N) kidney homogenate in CFA displayed no anti-TBM reaction. This is in perfect correlation with the absence of TIN and anti-TBM reaction in chronically rejected BP kidneys grafted to BN.1B (RT1b-identical) recipients. In accord with the literature data, LEW.1N animals carrying no TBM antigen(s) did not develop anti-TBM reaction detectable on their own kidneys following BP.1N immunization. In our experiments the adjuvant effect of alloantigenic difference was necessary for the immunization with syngeneic BN kidney and CFA did not induce any anti-TBM signs in BN recipients' own kidneys. The existence of some anti-TBM antigen Ir genes linked to the rat MHC can thus be assumed. However, there was no clear-cut association of glomerular changes with MHC in immunization experiments. On the basis of the data presented here the contribution of an anti-TBM component and TIN to the subacute rejection of RT1n-matched rat kidney grafts seems to be confirmed in the special (BP.1N to BN) strain combination previously described.
PubMed ID
6416897 View in PubMed
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Newborn and adult recombinant inbred strains: a tool to search for genetic determinants of target organ damage in hypertension.

https://arctichealth.org/en/permalink/ahliterature52979
Source
Kidney Int. 1998 Jun;53(6):1488-92
Publication Type
Article
Date
Jun-1998
Author
P. Hamet
Z. Pausova
P. Dumas
Y L Sun
J. Tremblay
M. Pravenec
J. Kunes
D. Krenova
V. Kren
Author Affiliation
Centre de Recherche du C.H.U.M, Université de Montréal, Québec, Canada. hamet@ere.umontreal.ca
Source
Kidney Int. 1998 Jun;53(6):1488-92
Date
Jun-1998
Language
English
Publication Type
Article
Keywords
Aging - physiology
Animals
Animals, Newborn - genetics - growth & development - physiology
Blood Pressure - physiology
Genome
Hypertension - complications - genetics
Kidney - pathology
Kidney Diseases - etiology - genetics - pathology
Organ Size - physiology
Phenotype
Quantitative Trait, Heritable
Rats
Rats, Inbred SHR - physiology
Recombination, Genetic
Research Support, Non-U.S. Gov't
Abstract
It has been proposed that one of the primary events in the development of essential hypertension is a growth-related process initiated as early as during fetal development. Differences in kidney size have been observed between most rat models of hypertension and their respective controls. In this study, we analyzed relative kidney size (kidney weight/body wt) in a set of rat recombinant inbred strains (RIS) (N = 27) and their progenitors, the spontaneously hypertensive rat strain (SHR/Ola) and Brown Norway congenic strain (BN.1x), at two different ages, at birth and at 15 weeks. In the progenitors, the relative kidney weight was higher in the hypertensive than in the normotensive strain of both the newborn (P
PubMed ID
9607180 View in PubMed
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Questions concerning the significance of a close linkage between morphogenetic (1x) and histocompatibility (H-5) loci in the Norway rat.

https://arctichealth.org/en/permalink/ahliterature27353
Source
Folia Morphol (Praha). 1980;28(1):24-7
Publication Type
Article
Date
1980

The significance of genetic factors for thalidomide teratogenicity in the Norway rat.

https://arctichealth.org/en/permalink/ahliterature65365
Source
Acta Univ Carol [Med] (Praha). 1989;35(1-2):3-10
Publication Type
Article
Date
1989
Author
V. Bílá
V. Kren
Source
Acta Univ Carol [Med] (Praha). 1989;35(1-2):3-10
Date
1989
Language
English
Publication Type
Article
Keywords
Animals
Bone Diseases, Developmental - chemically induced
Female
Male
Rats
Rats, Inbred BN
Rats, Inbred Lew
Teratogens
Thalidomide
Abstract
Thalidomide teratogenicity was tested on a model based on the system of congenic strains of the laboratory rat, including the mutant allele lx, which determines the polydactyly-luxate syndrome. The phenotypic expression of the allele lx changes according to the genetic background of the carrier and also according to factors of the external environment. On a hybrid genetic background LEW/BN the allele lx acts as recessive, and heterozygotes +/lx are unaffected. In a number of experiments it was proved, however, that these hybrids (LEW/BN, +/lx) had an increased sensitivity to the induction of limb malformations (polydactyly, tibial hemimelia, oligodactyly) by various teratogens. Thalidomide was administered on the 12th day of pregnancy by the intraperitoneal route in a mixture of Tween 20 with saline (1:3) in doses of 25, 50 and 200 mg/kg to females with genetic background LEW that were purposely mated with males of the BN or BN.lx strains. The produced progeny had genotypes LEW/BN, +/+ or LEW/BN, +/lx. In offsprings that had in the genotype the mutant allele lx in a heterozygous condition (+/lx) preaxial polydactyly of hind limbs developed after all the thalidomide doses tested. This malformation occurred in 17 out of 18 litters, altogether in 97 out of 162 foetuses +/lx, i.e. in 59.9%. In the progeny without the mutant allele (genotype +/+) polydactyly did not develop in any of the 108 cases. Control foetuses +/+ the mothers of which had been administered only Tween 20 with saline remained unaffected, while in control foetuses +/lx polydactyly developed in 8.1% (3 cases). The result demonstrates thalidomide teratogenicity in the laboratory rat where it has not been proved unambiguously so far. The teratogenic effect is the outcome of the interaction of thalidomide with the mutant allele lx. At the same time there is emphasized the importance of the genotype of the experimental animals in the testing of teratogens.
PubMed ID
2491005 View in PubMed
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11 records – page 1 of 2.