Genetic mouse models of Parkinsonism: Strengths and limitations

被引：117

作者：

Fleming S.M. ^{[1
]}

Fernagut P.-O. ^{[1
]}

Chesselet M.-F. ^{[1
,2
]}

机构：

[1] Department of Neurology, David Geffen School of Medicine, UCLA, Los Angeles

[2] Department of Neurology, David Geffen School of Medicine, UCLA, Los Angeles, CA 90095-1769

来源：

NeuroRX | 2005年 / 2卷 / 3期

关键词：

DJ-1; Mice; Nurr1; Parkin; Pitx3; α-Synuclein;

D O I：

10.1602/neurorx.2.3.495

中图分类号：

学科分类号：

摘要：

Parkinson's disease (PD) is a progressive neurodegenerative disorder. Patients with PD display a combination of motor symptoms including resting tremor, rigidity, bradykinesia, and postural instability that worsen over time. These motor symptoms are related to the progressive loss of dopamine neurons in the substantia nigra pars compacta. PD patients also suffer from nonmotor symptoms that may precede the cardinal motor symptoms and that are likely related to pathology in other brain regions. Traditional toxin models of PD have focused on the nigrostriatal pathway and the loss of dopamine neurons in this region, and these models have been important in our understanding of PD and in the development of symptomatic treatments for the disease. However, they are limited in that they do not reproduce the full pathology and progression seen in PD, thus creating a need for better models. The recent discovery of specific genes causing familial forms of PD has contributed to the development of novel genetic mouse models of PD. This review discusses the validity, benefits, and limitations of these new models. © The American Society for Experimental NeuroTherapeutics, Inc.

引用

页码：495 / 503

页数：8

共 85 条

[1] Stiasny-Kolster K., Doerr Y., Moller J.C., Hoffken H., Behr T.M., Oertel W.H., Mayer G., Combination of "idiopathic" REM sleep behaviour disorder and olfactory dysfunction as possible indicator for α-synucleinopathy demonstrated by dopamine transporter FPCIT-SPECT, Brain, 128, pp. 126-137, (2005)
[2] Ponsen M.M., Stoffers D., Booij J., Van Eck-Smit B.L., Wolters E., Berendse H.W., Idiopathic hyposmia as a preclinical sign of Parkinson's disease, Ann Neurol, 56, pp. 173-181, (2004)
[3] Becker G., Muller A., Braune S., Buttner T., Benecke R., Greulich W., Klein W., Mark G., Rieke J., Thumler R., Early diagnosis of Parkinson's disease, J Neurol, 249, SUPPL. 3, (2002)
[4] Bonifati V., Rizzu P., Van Baren M.J., Schaap O., Breedveld G.J., Krieger E., Dekker M.C., Squitieri F., Ibanez P., Joosse M., Van Dongen J.W., Vanacore N., Van Swieten J.C., Brice A., Meco G., Van Duijn C.M., Oostra B.A., Heutink P., Mutations in the DJ-1 gene associated with autosomal recessive early-onset parkinsonism, Science, 299, pp. 256-259, (2003)
[5] Kitada T., Asakawa S., Hattori N., Matsumine H., Yamamura Y., Minoshima S., Yokochi M., Mizuno Y., Shimizu N., Mutations in the parkin gene cause autosomal recessive juvenile parkinsonism, Nature, 392, pp. 605-608, (1998)
[6] Kruger R., Kuhn W., Muller T., Woitalla D., Graeber M., Kosel S., Przuntek H., Epplen J.T., Schols L., Riess O., Ala30Pro mutation in the gene encoding α-synuclein in Parkinson's disease, Nat Genet, 18, pp. 106-108, (1998)
[7] Leroy E., Anastasopoulos D., Konitsiotis S., Lavedan C., Polymeropoulos M.H., Deletions in the Parkin gene and genetic heterogeneity in a Greek family with early onset Parkinson's disease, Hum Genet, 103, pp. 424-427, (1998)
[8] Polymeropoulos M.H., Lavedan C., Leroy E., Ide S.E., Dehejia A., Dutra A., Pike B., Root H., Rubenstein J., Boyer R., Stenroos E.S., Chandrasekharappa S., Athanassiadou A., Papapetropoulos T., Johnson W.G., Lazzarini A.M., Duvoisin R.C., Di Iorio G., Golbe L.I., Nussbaum R.L., Mutation in the α-synuclein gene identified in families with Parkinson's disease, Science, 276, pp. 2045-2047, (1997)
[9] Singleton A.B., Farrer M., Johnson J., Singleton A., Hague S., Kachergus J., Hulihan M., Peuralinna T., Dutra A., Nussbaum R., Lincoln S., Crawley A., Hanson M., Maraganore D., Adler C., Cookson M.R., Muenter M., Baptista M., Miller D., Blancato J., Hardy J., Gwinn-Hardy K., α-synuclein locus triplication causes Parkinson's disease, Science, 302, (2003)
[10] Wintermeyer P., Kruger R., Kuhn W., Muller T., Woitalla D., Berg D., Becker G., Leroy E., Polymeropoulos M., Berger K., Przuntek H., Schols L., Epplen J.T., Riess O., Mutation analysis and association studies of the UCHL1 gene in German Parkinson's disease patients, Neuroreport, 11, pp. 2079-2082, (2000)

← 1 2 3 4 5 6 7 8 9 →