期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2004
卷号：101
期号：12
页码：4198-4203
DOI：10.1073/pnas.0400131101
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：The Prnp gene encodes the cellular prion protein PrPC. Removal of its ORF does not result in pathological phenotypes, but deletions extending into the upstream intron result in cerebellar degeneration, possibly because of ectopic cis-activation of the Prnd locus that encodes the PrPC homologue Doppel (Dpl). To test this hypothesis, we removed Prnd from Prnpo/o mice by transallelic meiotic recombination. Balanced loxP-mediated ablation yielded mice lacking both PrPC and Dpl (Prno/o), which developed normally and showed unimpaired immune functions but suffered from male infertility. However, removal of the Prnd locus abolished cerebellar degeneration, proving that this phenotype is caused by Dpl upregulation. The absence of compound pathological phenotypes in Prno/o mice suggests the existence of alternative compensatory mechanisms. Alternatively, Dpl and PrPC may exert distinct functions despite having partly overlapping expression profiles.
