Reference SummaryHernandez-Porras I, Rare Dis 2015;3(1):e1045169

Title

The impact of the genetic background in the Noonan syndrome phenotype induced by K-Ras(V14I).

Authors

Hernandez-Porras I; Jimenez-Catalan B; Schuhmacher AJ; Guerra C

Journal

Rare Dis

Volume

Issue

Year

2015

Pages

e1045169

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.

Links

J:239870 – MGI References
26458870 – National Library of Medicine/PubMed

Strain Notes

Strain	Note
129S2.129-Kras^tm4.1Bbd	These mice had been backcrossed onto C57BL/6JOlaHsd at least 7 generations.
B6.129-Kras^tm4.1Bbd	These mice had been backcrossed onto C57BL/6JOlaHsd at least 7 generations. Without treatment in utero, these mice die perinatally.
B6.129-Kras^tm4.1Bbd/+	These mice had been backcrossed onto C57BL/6JOlaHsd at least 7 generations.

Models
Strain	Model Name	Treatment Agent(s)	Organ Affected	Frequency
B6;129-Kras^tm4.1Bbd	Leukocyte - Myelocyte (Granulocyte) hyperplasia		Spleen	observed
B6.129-Kras^tm4.1Bbd/+	Leukocyte - Myelocyte (Granulocyte) hyperplasia		Spleen	observed
B6.129-Kras^tm4.1Bbd	Leukocyte - Myelocyte (Granulocyte) hyperplasia	PD0325901 (MEK inhibitor)	Spleen	observed
129S2.129-Kras^tm4.1Bbd	Leukocyte - Myelocyte (Granulocyte) hyperplasia		Spleen	observed