NR AXVX
AU Schiebel,K.; Kashkevich,K.; Orlicz-Welcz,B.; Henz,I.
TI Bovine Prion Protein Gene Expression is Modulated by DNA Polymorphisms in the Promoter Region
QU International Conference - Prion 2007 (26.-28.9.2007) Edinburgh International Conference Centre, Edinburgh, Scotland, UK - Book of Abstracts: Epidemiology, Risk Assessment and Transmission P04.107
IA http://www.prion2007.com/pdf/Prion Book of Abstracts.pdf
PT Konferenz-Poster
AB
The observation that prion protein gene knock out mice (Prnp-/-) can not be infected with prions and that mice with a single copy of Prnp (Prnp+/-) have a much longer incubation time than normal mice resulted in the hypothesis that prion infection depends on endogenous expression of the prion protein and that incubation time correlates with the amount of prion protein expressed. This hypothesis was further confirmed in transgenic mice with an additional Prnp copy resulting in a shorter incubation time.
DNA polymorphisms in the bovine PRNP promoter were found in known transcription factor binding sites. To study the influence of 13 polymorphisms within the core promoter on prion protein gene expression, naturally occurring combinations were cloned into luciferase expression vectors and transfected into Neuro2A cells as well as into primary hippocampal cells. A specific haplotype B resulted in a significant lower expression level than all other constructs. Interestingly, this haplotype was underrepresented in German cows tested positive for BSE, indicating that reduced expression of the bovine PRNP gene also leads to a reduced risk acquire BSE.
To test which polymorphic position within the prion promoter region is underlying the reduced expression, serial mutations were introduced in existing constructs, transfected into Neuro2A cells and analysed for expression. No single polymorphism could be identified to have major influence. Expression seems to be strongly influenced by the combination of several SNPs.
AD K. Schiebel, K. Kashkevich, B. Orlicz-Welcz, I. Henz, Institute für Biochemistry, Germany
SP englisch
PO Schottland