title: The impact of the genetic background in the Noonan syndrome phenotype induced by K-Ras(V14I).
abstract: Noonan syndrome (NS) is an autosomal dominant genetic disorder characterized by short stature, craniofacial dysmorphism, and congenital heart defects. A significant fraction of NS-patients also develop myeloproliferative disorders. The penetrance of these defects varies considerably among patients. In this study, we have examined the effect of 2 genetic backgrounds (C57BL/6J.OlaHsd and 129S2/SvPasCrl) on the phenotypes displayed by a mouse model of NS induced by germline expression of the mutated K-Ras (V14I) allele, one of the most frequent NS-KRAS mutations. Our results suggest the presence of genetic modifiers associated to the genetic background that are essential for heart development and function at early stages of postnatal life as well as in the severity of the haematopoietic alterations.
authors.affiliation: Molecular Oncology; Centro Nacional de Investigaciones Oncológicas (CNIO) ; Madrid, Spain.
authors.forename: Isabel
authors.initials: I
authors.lastname: Hernández-Porras
authors.affiliation: Molecular Oncology; Centro Nacional de Investigaciones Oncológicas (CNIO) ; Madrid, Spain.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Jiménez-Catalán
authors.affiliation: Molecular Oncology; Centro Nacional de Investigaciones Oncológicas (CNIO) ; Madrid, Spain.
authors.forename: Alberto J
authors.initials: AJ
authors.lastname: Schuhmacher
authors.affiliation: Molecular Oncology; Centro Nacional de Investigaciones Oncológicas (CNIO) ; Madrid, Spain.
authors.forename: Carmen
authors.initials: C
authors.lastname: Guerra
keywords: Noonan Syndrome; Ras oncogenes; Rasopathies; developmental disorders; genetic backgrounds; genotype-phenotype correlation; modifiers; mouse models