Related Experiment Video
Updated: Jun 16, 2026
Inchworming: A Novel Motor Stereotypy in the BTBR T+ Itpr3tf/J Mouse Model of Autism
Published on: July 5, 2014
Behavioural and cognitive abnormalities in an imprinting centre deletion mouse model for Prader-Willi syndrome
Dinko Relkovic1, Christine M Doe, Trevor Humby
1Laboratory of Cognitive and Behavioural Neuroscience, The Babraham Institute, Babraham Research Campus, Cambridge, UK.
Insights
Mice with Prader-Willi syndrome (PWS) genetic disruptions showed impaired attention and cognitive deficits, mirroring human PWS conditions. These findings highlight the role of chromosome 15q11-q13 imprinted genes in neurodevelopment and behavior.
Area of Science:
- Neurogenetics
- Developmental Neuroscience
- Behavioral Genetics
Background:
- Imprinted genes on chromosome 15q11-q13 are implicated in psychiatric disorders like schizophrenia and autism.
- Disruptions in this region cause Prader-Willi syndrome (PWS), a neurodevelopmental disorder characterized by failure to thrive, learning disabilities, overeating, and behavioral issues.
- PWS is associated with frontal lobe dysfunction, affecting cognitive and behavioral phenotypes.
Purpose of the Study:
- To investigate the contribution of imprinted genes in the 15q11-q13 region to psychological and behavioral phenotypes.
- To utilize the Prader-Willi syndrome imprinting center deletion mouse model (PWS-IC(+/-)) to study these effects.
- To assess the impact on attention, response control, and other behavioral measures.
Main Methods:
- Utilized the PWS-IC(+/-) mouse model.
- Employed the five-choice serial reaction time task (5-CSRTT) to assess visuospatial attention and response control.
- Assessed locomotor activity, open-field behavior, and sensorimotor gating (acoustic startle and prepulse inhibition).
Main Results:
- PWS-IC(+/-) mice exhibited reduced locomotor activity, increased acoustic startle responses, and decreased prepulse inhibition.
- In the 5-CSRTT, these mice showed deficits in accuracy, longer reaction times, and increased omissions, indicating impaired attention.
- Task manipulations corroborated the attention-based deficits.
Conclusions:
- The PWS-IC(+/-) mouse model recapitulates key aspects of the PWS clinical condition, including frontal dysfunction.
- These findings suggest that imprinted genes within the 15q11-q13 region contribute significantly to general behavioral and cognitive function.
- This study provides insights into the genetic underpinnings of neurodevelopmental and psychiatric disorders associated with this imprinted locus.
Abstract:
The genes in the imprinted cluster on human chromosome 15q11-q13 are known to contribute to psychiatric conditions such as schizophrenia and autism. Major disruptions of this interval leading to a lack of paternal allele expression give rise to Prader-Willi syndrome (PWS), a neurodevelopmental disorder with core symptoms of a failure to thrive in infancy and, on emergence from infancy, learning disabilities and over-eating. Individuals with PWS also display a number of behavioural problems and an increased incidence of neuropsychiatric abnormalities, which recent work indicates involve aspects of frontal dysfunction. To begin to examine the contribution of genes in this interval to relevant psychological and behavioural phenotypes, we exploited the imprinting centre (IC) deletion mouse model for PWS (PWS-IC(+/-)) and the five-choice serial reaction time task (5-CSRTT), which is primarily an assay of visuospatial attention and response control that is highly sensitive to frontal manipulations. Locomotor activity, open-field behaviour and sensorimotor gating were also assessed. PWS-IC(+/-) mice displayed reduced locomotor activity, increased acoustic startle responses and decreased prepulse inhibition of startle responses. In the 5-CSRTT, the PWS-IC(+/-) mice showed deficits in discriminative response accuracy, increased correct reaction times and increased omissions. Task manipulations confirmed that these differences were likely to be due to impaired attention. Our data recapitulate several aspects of the PWS clinical condition, including findings consistent with frontal abnormalities, and may indicate novel contributions of the imprinted genes found in 15q11-q13 to behavioural and cognitive function generally.
