Abstract:
:Prader-Willi syndrome (PWS) and Angelman syndrome (AS) result from the loss of function of imprinted genes in human chromosome 15q11-q13. The central part of mouse chromosome 7 is homologous to human 15q11-q13, with conservation of both gene order and imprinted features. We report here the characterization of a transgene insertion (Epstein-Barr virus Latent Membrane Protein 2A, LMP2A) into mouse chromosome 7C, which has resulted in mouse models for PWS and AS dependent on the sex of the transmitting parent. Epigenotype (allelic expression and DNA methylation) and fluorescence in situ hybridization analyses indicate that the transgene-induced mutation has generated a complete deletion of the PWS/AS-homologous region but has not deleted flanking loci. Because the intact chromosome 7, opposite the deleted homolog, maintains the correct imprint in somatic cells of PWS and AS mice and establishes the correct imprint in male and female germ cells of AS mice, homologous association and replication asynchrony are not part of the imprinting mechanism. This heritable-deletion mouse model will be particularly useful for the identification of the etiological genes and mechanisms, phenotypic basis, and investigation of therapeutic approaches for PWS.
journal_name
Proc Natl Acad Sci U S Aauthors
Gabriel JM,Merchant M,Ohta T,Ji Y,Caldwell RG,Ramsey MJ,Tucker JD,Longnecker R,Nicholls RDdoi
10.1073/pnas.96.16.9258keywords:
subject
Has Abstractpub_date
1999-08-03 00:00:00pages
9258-63issue
16eissn
0027-8424issn
1091-6490journal_volume
96pub_type
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