Comparative Behavioral and Proteomic Analysis of Rat Snrprn and Magel2 Models

Funding Summary

Two genes disrupted in PWS are SNRPN and MAGEL2, the latter which is the causal gene for Schaaf-Yang syndrome (SYS). The goal of this study is to identify and compare behavioral characteristics and protein profiles of rat models that are deficient for Snrpn and Magel2. These studies will not only provide us a deeper understanding of neurobehavior, organ physiology and changes occurring at the molecular level in these rats, but also provide a great tool for future preclinical studies that may require much needed meaningful biomarkers and outcome measures and will also enable us to identify potential therapeutic interventions.

Lay Abstract

Prader-Willi syndrome (PWS) is a genomic imprinting disorder resulting from deletions of paternally expressed genes on chromosome 15q11-13. Two genes often disrupted in PWS are SNRPN and MAGEL2, the latter which is the causal gene for Schaaf-Yang syndrome (SYS), a sister disorder to PWS with overlapping and unique clinical features. The goal of this study is to identify and compare behavioral phenotypes and protein profiles of laboratory rat models that are deficient for Snrpn and Magel2. These rat models not only provide us a tool to better understand the human condition, but also enable us to identify potential therapeutic interventions. Since patients with PWS exhibit a wide range of behavioral symptoms, we will examine the effects of Snrpn absence on neurobehavioral outcomes using well-established tests for locomotor activity, anxiety-like behaviors, sociability and cognitive function at two different developmental time points which will help us understand the progression of the disease. In additional to behavior assessments, we will also assess peripheral physiological outcome measures to determine if these features are disrupted in rats lacking Snrpn, similar to what is observed in patients with PWS. To understand molecular changes associated with the observed phenotypes we will perform proteomic profiling to identify molecular biomarker signatures in brain tissue of these rats deficient for paternally expressed Snrpn and Magel2 imprinted genes. These studies will not only provide us a deeper understanding of neurobehavior, organ physiology and changes occurring at the molecular level in these rats, but also provide a great tool for future preclinical studies that may require much needed meaningful biomarkers and outcome measures.

Funded Year:

2021

Awarded to:

Rodney Samaco, Ph.D.

Amount:

$108,000

Institution:

Baylor College of Medicine

Researcher:

Rodney Samaco, Ph.D.

Search Projects

Donate for PWS Research