Related Experiment Videos
A mouse model for Prader-Willi syndrome imprinting-centre mutations
T Yang1, T E Adamson, J L Resnick
1Department of Molecular Genetics and Microbiology, University of Florida Brain Institute, University of Florida College of Medicine, Gainesville 32610-0266, USA.
Nature Genetics
|May 20, 1998
Summary
Prader-Willi syndrome (PWS) is linked to the 15q11-q13 imprinting center (IC). Mouse models show that deletions affecting the IC, not just SNRPN, cause PWS-like phenotypes, confirming conserved imprinting mechanisms.
Area of Science:
- Genetics
- Developmental Biology
- Genomic Imprinting
Background:
- The 15q11-q13 region harbors an imprinting center (IC) crucial for regulating gene expression.
- Deletion of the IC can lead to Prader-Willi syndrome (PWS), a complex genetic disorder.
Purpose of the Study:
- To investigate the role of the imprinting center (IC) in the 15q11-q13 region.
- To develop and characterize mouse models for understanding Prader-Willi syndrome (PWS) pathogenesis.
- To elucidate the mechanism of coordinate gene expression regulated by the IC.
Main Methods:
- Creation of two distinct mouse deletion models targeting the Snrpn gene and the putative PWS-IC.
- Phenotypic analysis of mutant mice.
- Assessment of imprinted gene expression (Zfp127, Ndn, Ipw) in the affected genomic region.
Main Results:
- Mice with intragenic deletions in Snrpn remained phenotypically normal, indicating SNRPN mutations alone are insufficient for PWS.
- Mice with larger deletions encompassing Snrpn and the PWS-IC exhibited loss of Zfp127, Ndn, and Ipw expression.
- These mice displayed phenotypes consistent with human PWS infants.
Conclusions:
- The imprinting center (IC) in the 15q11-q13 region is essential for regulating the expression of multiple imprinted genes.
- The function and positional importance of the IC are conserved between mice and humans.
- Mouse models are valuable for studying the molecular mechanisms underlying imprinting and PWS.