RESUMO
We have previously reported a quantitative trait locus associated with pressure-independent cardiac hypertrophy in the spontaneously hypertensive rat (SHR) of the Okamoto strain. This locus (Lvm1; left ventricular mass locus 1) contains the gene Fgf2 that codes for the potent cardiac growth factor, Fibroblast Growth Factor 2 (FGF2). Given that FGF2 appears essential for the induction of certain forms of cardiac hypertrophy in the rat, we proposed this gene as a candidate for the cardiac enlargement seen in the SHR. Previous reports of elevated FGF2 mRNA levels in the SHR, led us to hypothesise that nucleotide sequence variations occurring in the coding regions or in putative transcriptional factor binding sites within the Fgf2 promoter might play a role in cardiac hypertrophy in this strain. Given that we have also recently derived from the SHR a rat strain that develops spontaneous cardiac hypertrophy in the absence of hypertension (the Hypertrophic Heart Rat; HHR), we also took the opportunity to examine the sequence of its Fgf2 promoter and coding region. However, extensive sequence analysis of the promoter and coding regions of the SHR and HHR Fgf2 genes failed to reveal any nucleotide variations between strains. Thus, we conclude that variations in the nucleotide sequence of the promoter and coding region of the SHR Fgf2 gene do not play a role in the cardiac hypertrophy of the SHR and HHR strains.
Assuntos
Cardiomegalia/genética , Fator 2 de Crescimento de Fibroblastos/genética , Hipertensão/genética , Animais , Sequência de Bases , Reação em Cadeia da Polimerase , Regiões Promotoras Genéticas/genética , Ratos , Ratos Endogâmicos SHR , Análise de Sequência de DNARESUMO
The amplified fragment length polymorphism (AFLP) technique has been used to enhance marker density in a large set of recombinant inbred strains (H x B and B x H) derived from a spontaneously hypertensive rat (SHR/OlaIpcv) and a Brown-Norway (BN.lx/Cub) inbred strain. Thirteen different primer combinations were tested and a total of 191 polymorphic bands were detected. From these polymorphic bands 89 AFLP markers could be assigned to specific chromosomes. Several of these AFLP markers were mapped to regions with low marker density, thus filling up gaps in the existing genetic map of these recombinant inbred strains. These results substantiate the value of the AFLP technology in increasing marker density in genetic maps.
Assuntos
Mapeamento Cromossômico , Marcadores Genéticos , Polimorfismo de Fragmento de Restrição , Ratos Endogâmicos/genética , Animais , Cruzamentos Genéticos , Desoxirribonuclease EcoRI/genética , Desoxirribonucleases de Sítio Específico do Tipo II/genética , Feminino , Ligação Genética , Masculino , Polimorfismo Genético , Ratos , Ratos Endogâmicos BN , Ratos Endogâmicos SHRRESUMO
Abnormalities in carbohydrate and lipid metabolism are common in patients with essential hypertension and in the spontaneously hypertensive rat (SHR). To identify chromosome regions contributing to this clustering of cardiovascular risk factors in the SHR, we searched for quantitative trait loci (QTL) associated with insulin resistance, glucose intolerance, and dyslipidemia by using the HXB/BXH recombinant inbred (RI) strains. Analysis of variance in RI strains suggested significant effects of genetic factors. A genome screening of the RI strains with more than 700 markers revealed QTL significantly associated with insulin resistance on Chromosomes (Chrs) 3 and 19. The Chr 19 QTL was confirmed by testing a previously derived SHR-19 congenic strain: transfer of a Chr 19 segment delineated by markers D19Rat57 and D19Mit7 from the Brown Norway (BN/Cr) strain onto the genetic background of the SHR/Ola was associated with decreased insulin and glucose concentrations and ameliorated insulin resistance at the tissue level. These findings suggest that closely linked genes on Chr 19, or perhaps even a single gene with pleiotropic effects, influence the clustering of metabolic disturbances in the SHR-BN model.
