Cardioprotective actions of cyclic GMP: lessons from genetic animal models

Abstract

Most common diseases and/or their consequences, including hypertension and susceptibility to end-organ damage, have genetic components. Contrary to hereditary Mendelian diseases (where the existence of a rare mutation within a single gene usually dictates whether signs of the disease are present), the manifestations of common diseases correspond to what is defined in genetics as “quantitative complex traits”. Such traits show within populations continuous variation from low to high values, and are shaped by the interactions of a great number of genes (each typically having small effects on their own) with environmental factors. Consequently, identification of genetic variants contributing to complex traits must rely on methods that are different than those used for the identification of Mendelian genetic mutations (which can be performed by following within pedigrees the hereditary transmission of markers linked to the mutated gene). Among several available tools, genetic animal models have proved particularly useful to identify the effects of naturally occurring genetic variants and their effects within mammalian organisms. Indeed, inbred strains are organisms that carry identical copies of each gene. Accordingly, it is possible by performing crosses between them to reduce the complexity of the problem, since the progeny of crosses will carry only 2 possible variants of any gene and experimental and environmental conditions can be controlled.