title: Influence of different promoters on the expression pattern of mutated human alpha-synuclein in transgenic mice.
abstract: Two missense mutations (A53T and A30P) in the gene encoding the presynaptic protein alpha-synuclein (asyn) are associated with rare, dominantly inherited forms of Parkinson's disease (PD) and its accumulation in Lewy bodies and Lewy neurites. As an initial step in investigating the role of asyn in the pathogenesis of PD, we have generated C57BL/6 transgenic mice overexpressing the doubly mutated human asyn under the control of three different promoters; the chicken beta-actin (chbetaactin), the mouse tyrosine hydroxylase 9.6 kb (msTH) and the mouse prion protein (msprp). In this study we compared the regional and cellular expression pattern of the transgenic protein in the brain and peripheral organs of various transgenic mouse lines. Western blot analysis and immunohistochemistry consistently showed that all three promoters successfully drive the expression of the transgene. The msprp promoter was found to give the highest level of transgene expression. All promoters directed the expression into the brain and specific neuron types. However, the promoters differed with respect to (i) the expression pattern in peripheral organs, (ii) the number and (iii) the regional distribution of expressing cells in the brain. Furthermore, remarkable line-to-line variation of expression patterns was observed in mouse lines carrying the same construct. Future studies will analyze how the variations in transgene expression affect the pathogenesis in the animals.
authors.affiliation: Animal Physiology, Ruhr University Bochum, Bochum, Germany.
authors.forename: Lyutha
authors.initials: L
authors.lastname: Maskri
authors.forename: XinRan
authors.initials: X
authors.lastname: Zhu
authors.forename: Sabrina
authors.initials: S
authors.lastname: Fritzen
authors.forename: Kati
authors.initials: K
authors.lastname: Kühn
authors.forename: Christoph
authors.initials: C
authors.lastname: Ullmer
authors.forename: Peter
authors.initials: P
authors.lastname: Engels
authors.forename: Michael
authors.initials: M
authors.lastname: Andriske
authors.forename: Christine C
authors.initials: CC
authors.lastname: Stichel
authors.forename: Hermann
authors.initials: H
authors.lastname: Lübbert
mesh_terms: D000199:Actins / Q000235:genetics; D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D001923:Brain Chemistry / Q000235:genetics; D019556:COS Cells; D002645:Chickens / Q000235:genetics; D002522:Chlorocebus aethiops; D005786:Gene Expression Regulation / Q000235:genetics*; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D020125:Mutation, Missense / Q000235:genetics; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D010300:Parkinson Disease / Q000235:genetics; D011328:Prions / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics*; D019076:Transgenes / Q000235:genetics*; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics; D051844:alpha-Synuclein / Q000235:genetics*
chemical_list: D000199:Actins; D011328:Prions; D051844:alpha-Synuclein; D014446:Tyrosine 3-Monooxygenase