Abnormal Igf2 gene in Prague hereditary hypertriglyceridemic rats: its relation to blood pressure and plasma lipids
Language English Country Netherlands Media print-electronic
Document type Comparative Study, Journal Article, Research Support, Non-U.S. Gov't
- MeSH
- Genetic Linkage MeSH
- Genotype MeSH
- Hypertriglyceridemia blood genetics pathology physiopathology MeSH
- Rats, Inbred Strains MeSH
- Insulin-Like Growth Factor II genetics MeSH
- Blood Pressure physiology MeSH
- Crosses, Genetic MeSH
- Rats MeSH
- Kidney anatomy & histology MeSH
- Lipids blood MeSH
- Microsatellite Repeats MeSH
- DNA Mutational Analysis MeSH
- Rats, Inbred Lew MeSH
- Heart anatomy & histology MeSH
- Body Weight genetics MeSH
- Organ Size genetics MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Male MeSH
- Female MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Comparative Study MeSH
- Names of Substances
- Insulin-Like Growth Factor II MeSH
- Lipids MeSH
Prague hypertriglyceridemic (HTG) rats represent a suitable model of metabolic syndrome. We have established the set of F(2) hybrids derived from HTG and Lewis progenitors to investigate the relationship between respective polymorphism(s) of Igf2 gene and blood pressure (BP) or other cardiovascular phenotypes. HTG rats had elevated systolic BP and plasma triglycerides but lower plasma cholesterol compared to Lewis rats of both genders. In males, there was higher mean arterial pressure, diastolic BP and relative heart weight in HTG than in Lewis rats. The results obtained in the total population of F(2) hybrids indicated strong segregation of Igf2 genotype with plasma triglycerides. There was no segregation of Igf2 genotype with any BP component except BP changes occurring after the blockade of either renin-angiotensin system (RAS) or NO synthase. When F(2) population was analyzed according to gender, male F(2) progeny homozygous for HTG Igf2 allele had significantly higher plasma triglycerides and greater BP changes after NO synthase blockade than those homozygous for Lewis allele. On the contrary, male F(2) progeny homozygous for HTG Igf2 allele had significantly lower plasma cholesterol and smaller BP changes after RAS blockade. PCR analysis of Igf2 gene by using of microsatelite D1Mgh22 has shown polymorphism between HTG and Lewis rats. Sequence analysis of cDNA revealed insertion of 14 nucleotides in HTG gene. In conclusion, polymorphism in Igf2 gene may be responsible for differences in lipid metabolism between HTG and Lewis rats. It remains to determine how these abnormalities could be involved in BP regulation by particular vasoactive systems.
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