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Recommendations for the investigation of animal models of Prader–Willi syndrome

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Abstract

Prader–Willi syndrome (PWS) occurs in about 1 in 15,000 individuals and is a contiguous gene disorder causing developmental disability, hyperphagia usually with obesity, and behavioral problems, including an increased incidence of psychiatric illness. The genomic imprinting that regulates allele-specific expression of PWS candidate genes, the fact that multiple genes are typically inactivated, and the presence of many genes that produce functional RNAs rather than proteins has complicated the identification of the underlying genetic pathophysiology of PWS. Over 30 genetically modified mouse strains that have been developed and characterized have been instrumental in elucidating the genetic and epigenetic mechanisms for the regulation of PWS genes and in discovering their physiological functions. In 2011, a PWS Animal Models Working Group (AMWG) was established to generate discussions and facilitate exchange of ideas regarding the best use of PWS animal models. Here, we summarize the goals of the AMWG, describe current animal models of PWS, and make recommendations for strategies to maximize the utility of animal models and for the development and use of new animal models of PWS.

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Acknowledgments

We thank the many researchers who contributed to the online survey of resources and needs in Animal Models of PWS. We also thank Dr. Theresa Strong, Scientific Director for the Foundation for Prader–Willi Research, and the participants at the Prader–Willi Syndrome Research Strategy Workshop, Mouse Models Workshop, held in Bethesda, MD, in November 2009. Grant sponsor was the Foundation for Prader–Willi Research (FPWR).

Disclosure

This report was commissioned by FPWR but FPWR made no contribution to the content of the report.

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Authors and Affiliations

  1. Department of Molecular Genetics and Microbiology, University of Florida College of Medicine, Gainesville, FL, USA

    James L. Resnick

  2. Division of Medical Genetics, Department of Pediatrics, Children’s Hospital of Pittsburgh of UPMC, Pittsburgh, PA, USA

    Robert D. Nicholls

  3. Department of Human Genetics, University of Pittsburgh School of Public Health, Pittsburgh, PA, USA

    Robert D. Nicholls

  4. Department of Medical Genetics, University of Alberta, Edmonton, AB, T6G 2H7, Canada

    Rachel Wevrick

Authors
  1. James L. Resnick
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  2. Robert D. Nicholls
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  3. Rachel Wevrick
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Corresponding author

Correspondence to Rachel Wevrick.

Electronic supplementary material

Below is the link to the electronic supplementary material.

335_2013_9454_MOESM1_ESM.pdf

Online Resource 1. Bibliography of research papers using mice with mutations in PWS-orthologous genes.Supplementary material 1 (PDF 60 kb)

335_2013_9454_MOESM2_ESM.pdf

Online Resource 2. Links to resource databases used by other Foundations focused on research on specific genetic diseases with developmental disability and/or obesity. Supplementary material 2 (PDF 133 kb)

335_2013_9454_MOESM3_ESM.pdf

Online Resource 3. Guidelines established for preclinical testing in animal models of other genetic diseases, Phenotyping Centers, and useful reference material for phenotypic testing in animals. Supplementary material 3 (PDF 64 kb)

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Resnick, J.L., Nicholls, R.D. & Wevrick, R. Recommendations for the investigation of animal models of Prader–Willi syndrome. Mamm Genome 24, 165–178 (2013). https://doi.org/10.1007/s00335-013-9454-2

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  • DOI: https://doi.org/10.1007/s00335-013-9454-2

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