Cognitive deficits in the Snord116 deletion mouse model for Prader-Willi syndrome

Anna Adhikari, Nycole A. Copping, Beth Onaga, Michael C. Pride, Rochelle L. Coulson, Mu Yang, Dag H. Yasui, Janine M LaSalle, Jill L Silverman

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Prader-Willi syndrome (PWS) is an imprinted neurodevelopmental disease caused by a loss of paternal genes on chromosome 15q11-q13. It is characterized by cognitive impairments, developmental delay, sleep abnormalities, and hyperphagia often leading to obesity. Clinical research has shown that a lack of expression of SNORD116, a paternally expressed imprinted gene cluster that encodes multiple copies of a small nucleolar RNA (snoRNA) in both humans and mice, is most likely responsible for many PWS symptoms seen in humans. The majority of previous research using PWS preclinical models focused on characterization of the hyperphagic and metabolic phenotypes. However, a crucial understudied clinical phenotype is cognitive impairments and thus we investigated the learning and memory abilities using a model of PWS, with a heterozygous deletion in Snord116. We utilized the novel object recognition task, which doesn't require external motivation, or exhaustive swim training. Automated findings were further confirmed with manual scoring by a highly trained blinded investigator. We discovered deficits in Snord116+/− mutant mice in the novel object recognition, location memory and tone cue fear conditioning assays when compared to age-, sex- matched, littermate control Snord116+/+ mice. Further, we confirmed that despite physical neo-natal developmental delays, Snord116+/− mice had normal exploratory and motor abilities. These results show that the Snord116+/− deletion murine model is a valuable preclinical model for investigating learning and memory impairments in individuals with PWS without common confounding phenotypes.

Original languageEnglish (US)
JournalNeurobiology of Learning and Memory
DOIs
StateAccepted/In press - Jan 1 2018

Fingerprint

Prader-Willi Syndrome
Aptitude
Phenotype
Small Nucleolar RNA
Learning
Hyperphagia
Multigene Family
Research
Fear
Cues
Motivation
Sleep
Obesity
Chromosomes
Research Personnel
Genes

Keywords

  • Animal model
  • Behavior
  • Cognitive
  • Genetics
  • Learning and memory
  • Neurodevelopment
  • Prader-Willi
  • Snord116

ASJC Scopus subject areas

  • Experimental and Cognitive Psychology
  • Cognitive Neuroscience
  • Behavioral Neuroscience

Cite this

Cognitive deficits in the Snord116 deletion mouse model for Prader-Willi syndrome. / Adhikari, Anna; Copping, Nycole A.; Onaga, Beth; Pride, Michael C.; Coulson, Rochelle L.; Yang, Mu; Yasui, Dag H.; LaSalle, Janine M; Silverman, Jill L.

In: Neurobiology of Learning and Memory, 01.01.2018.

Research output: Contribution to journalArticle

Adhikari, Anna ; Copping, Nycole A. ; Onaga, Beth ; Pride, Michael C. ; Coulson, Rochelle L. ; Yang, Mu ; Yasui, Dag H. ; LaSalle, Janine M ; Silverman, Jill L. / Cognitive deficits in the Snord116 deletion mouse model for Prader-Willi syndrome. In: Neurobiology of Learning and Memory. 2018.
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