Abstract
Prader-Willi syndrome (PWS) and Angelman syndrome (AS) result from the disturbance of imprinted gene expression within human chromosome 15q11–q13. Some cases of PWS and AS are caused by microdeletions near the SNRPN gene that disrupt a regulatory element termed the imprinting center (IC). The IC has two functional components; an element at the promoter of SNRPN involved in PWS (PWS-IC) and an element 35 kilobases (kb) upstream of SNRPN involved in AS (AS-IC). To further understand the function of the IC, we sought to create a mouse model for AS-IC mutations. We have generated two deletions at a location analogous to that of the human AS-IC. Neither deletion produced an imprinting defect as indicated by DNA methylation and gene expression analyses. These results indicate that no elements critical for AS-IC function in mouse reside within the 12.8-kb deleted region and suggest that the specific location of the AS-IC is not conserved between human and mouse.
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Acknowledgments
The authors thank Marisa Bartolomei for support and advice; Amanda DuBose and Chris Futtner for critical reading of the manuscript; Daniel Driscoll and Stormy Chamberlain for helpful discussion; Christine Kiefer and Thomas Yang for generously providing information on polymorphisms; Danielle Maatouk and Christine Kiefer for assistance with sodium bisulfite sequencing; and Jingda Shi in the Center for Mammalian Genetics at the University of Florida for sequencing. This work was supported by NIH grant GM55272 awarded to CIB. This work is dedicated to the memory of Camilynn Brannan.
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Camilynn I. Brannan was Deceased
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Peery, E.G., Elmore, M.D., Resnick, J.L. et al. A targeted deletion upstream of Snrpn does not result in an imprinting defect. Mamm Genome 18, 255–262 (2007). https://doi.org/10.1007/s00335-007-9019-3
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DOI: https://doi.org/10.1007/s00335-007-9019-3