Reznik DL, Yang MV, Albelda de la Haza P, Jain A, Spanjaard M, Theiss S, Schaaf CP, Malovannaya A, Strong TV, Veeraragavan S, Samaco RC
Dis Model Mech. 2023 Feb 1;16(2):dmm049829. doi: 10.1242/dmm.049829. Epub 2023 Feb 3. PMID: 36637363; PMCID: PMC9922728.
Previous studies in mice have utilized Magel2 gene deletion models to examine the consequences of its absence. We report the generation, molecular validation and phenotypic characterization of a novel rat model with a truncating Magel2 mutation modeling variants associated with Schaaf-Yang syndrome-causing mutations. Within the hypothalamus, a brain region in which human MAGEL2 is paternally expressed, we demonstrated, at the level of transcript and peptide detection, that rat Magel2 exhibits a paternal, parent-of-origin effect. In evaluations of behavioral features across several domains, juvenile Magel2 mutant rats displayed alterations in anxiety-like behavior and sociability measures. Moreover, the analysis of peripheral organ systems detected alterations in body composition, cardiac structure and function, and breathing irregularities in Magel2 mutant rats. Several of these findings are concordant with reported mouse phenotypes, indicating the conservation of MAGEL2 function across rodent species. Our comprehensive analysis revealing impairments across multiple domains demonstrates the tractability of this model system for the study of truncating MAGEL2 mutations.
Comparative Behavioral and Proteomic Analysis of Rat Snrprn and Magel2 Models
April 21, 2023