Magel2 Truncation Alters Select Behavioral and Physiological Outcomes in a Rat Model of Schaaf-Yang Syndrome

Authors

Derek L Reznik
Mingxiao V Yang
Pedro Albelda de la Haza
Antrix Jain
Melanie Spanjaard
Susanne Theiss
Christian P Schaaf
Anna Malovannaya
Theresa V Strong
Surabi Veeraragavan
Rodney C Samaco

Publication Date

2-1-2023

Journal

Disease Models & Mechanisms

DOI

10.1242/dmm.049829

PMID

36637363

PMCID

PMC9922728

PubMedCentral® Posted Date

2-3-2023

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes

Keywords

Humans, Rats, Mice, Animals, Proteins, Phenotype, Brain, Models, Biological, Antigens, Neoplasm, Schaaf-Yang syndrome, Prader-Willi syndrome, Magel2, Imprinting, Rat model

Abstract

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.

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