Common inbred strains of the laboratory rat can be divided into four different mitochondrial DNA haplotype groups represented by the SHR, BN, LEW, and F344 strains. In the current study, we investigated the metabolic and hemodynamic effects of the SHR vs. LEW mitochondrial genomes by comparing the SHR to a new SHR conplastic strain, SHR-mt(LEW); these strains are genetically identical except for their mitochondrial genomes. Complete mitochondrial DNA (mtDNA) sequence analysis comparing the SHR and LEW strains revealed gene variants encoding amino acid substitutions limited to a single mitochondrial enzyme complex, NADH dehydrogenase (complex I), affecting subunits 2, 4, and 5. Two of the variants in the mt-Nd4 subunit gene are located close to variants known to be associated with exercise intolerance and diabetes mellitus in humans. No variants were found in tRNA or rRNA genes. These variants in mt-Nd2, mt-Nd4, and mt-Nd5 in the SHR-mt(LEW) conplastic strain were linked to reductions in oxidative and nonoxidative glucose metabolism in skeletal muscle. In addition, SHR-mt(LEW) conplastic rats showed increased serum nonesterified fatty acid levels and resistance to insulin stimulated incorporation of glucose into adipose tissue lipids. These results provide evidence that inherited variation in mitochondrial genes encoding respiratory chain complex I subunits, in the absence of variation in the nuclear genome and other confounding factors, can influence glucose and lipid metabolism when expressed on the nuclear genetic background of the SHR strain.

• MeSH
• adeninnukleotidy metabolismus   MeSH
• dědičnost MeSH
• dietní sacharidy aplikace a dávkování   metabolismus   MeSH
• fenotyp MeSH
• fruktosa aplikace a dávkování   metabolismus   MeSH
• genetická variace * MeSH
• haplotypy MeSH
• hypertenze krev   enzymologie   genetika   patofyziologie   MeSH
• inzulin krev   MeSH
• inzulinová rezistence genetika   MeSH
• kosterní svaly enzymologie   MeSH
• krevní glukóza metabolismus   MeSH
• krevní tlak MeSH
• krysa rodu Rattus MeSH
• kyseliny mastné neesterifikované krev   MeSH
• mitochondriální DNA genetika   MeSH
• modely nemocí na zvířatech MeSH
• molekulární sekvence - údaje MeSH
• NADH-dehydrogenasa genetika   metabolismus   MeSH
• oxidativní fosforylace * MeSH
• potkani inbrední BN MeSH
• potkani inbrední F344 MeSH
• potkani inbrední LEW MeSH
• potkani inbrední SHR MeSH
• sekvence aminokyselin MeSH
• srdeční frekvence MeSH
• tuková tkáň enzymologie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• Názvy látek
• adeninnukleotidy MeSH
• dietní sacharidy MeSH
• fruktosa MeSH
• inzulin MeSH
• krevní glukóza MeSH
• kyseliny mastné neesterifikované MeSH
• mitochondriální DNA MeSH
• NADH dehydrogenase subunit 2, rat MeSH Prohlížeč
• NADH dehydrogenase subunit 4 MeSH Prohlížeč
• NADH dehydrogenase subunit 5, rat MeSH Prohlížeč
• NADH-dehydrogenasa MeSH

The spontaneously hypertensive rat (SHR) is the most widely used animal model of essential hypertension and associated metabolic disturbances. Multiple quantitative trait loci associated with hemodynamic and metabolic parameters have been mapped in the SHR. Recently, it has become possible to identify some of the specific quantitative trait gene (QTG) variants that underlie quantitative trait loci linked to complex cardiovascular and metabolic traits in SHR related strains. Recombinant inbred strains derived from SHR and Brown Norway progenitors, together with SHR congenic and transgenic strains, have proven useful for establishing the identity of several QTGs in SHR models. It is anticipated that the combined use of linkage analyses and gene expression profiles, together with the recently available genome sequences of both the SHR and Brown Norway strains and new methods for manipulating the rat genome, will soon accelerate progress in identifying QTGs for complex traits in SHR-related strains.

• MeSH
• exprese genu MeSH
• inbrední kmeny potkanů genetika   MeSH
• krysa rodu Rattus MeSH
• kvantitativní znak dědičný MeSH
• lokus kvantitativního znaku genetika   MeSH
• mapování chromozomů MeSH
• mitochondriální DNA genetika   MeSH
• potkani inbrední SHR genetika   MeSH
• potkani transgenní MeSH
• technika přenosu genů MeSH
• transposasy MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Research Support, N.I.H., Extramural MeSH
• Názvy látek
• mitochondriální DNA MeSH
• transposasy MeSH