Biochemical and morphological consequences of human α-synuclein expression in a mouse α-synuclein null background.
Biochemical and morphological consequences of human α-synuclein expression in a mouse α-synuclein null background.
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DOI：
10.1111/j.1460-9568.2010.07558.x
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发表时间：
2011-02
期刊：
影响因子：
--
通讯作者：
Richfield EK
中科院分区：
文献类型：
--
作者：
Prasad K;Tarasewicz E;Strickland PA;O'Neill M;Mitchell SN;Merchant K;Tep S;Hilton K;Datwani A;Buttini M;Mueller-Steiner S;Richfield EK
A consensus about the functions of human wild-type or mutated α-synuclein (αSYN) is lacking. Both forms of αSYN are implicated in Parkinson’s disease, whereas the wild-type form is implicated in substance abuse. Interactions with other cellular proteins and organelles may meditate its functions. We developed a series of congenic mouse lines containing various allele doses or combinations of the human wild type αSYN (hwαSYN) or a doubly mutated (A30P*A53T) αSYN (hm2αSYN) in a C57Bl/6J line spontaneously deleted in mouse αSYN (C57BL/6JOla). Both transgenes had a functional role in the nigrostriatal system, demonstrated by significant elevations in striatal catecholamines, metabolites, and the enzyme tyrosine hydroxylase compared to null-mice without a transgene. Consequences occurred when the transgenes were expressed at a fraction of the endogenous level. Hemizygous congenic mice did not exhibit any change in the number or size of dopaminergic neurons in the ventral midbrain at nine months of age. Human αSYN was predominantly located in neuronal cell bodies, neurites, synapses, and in intraneuronal/intraneuritic aggregates. The hm2αSYN transgene resulted in more aggregates and dystrophic neurites than did the hw5 transgene. The hwαSYN transgene resulted in higher expression of two striatal proteins, synaptogamin 7 and UCHL1, compared to the levels of the hm2αSYN transgene. These observations suggest that mutations in αSYN may impair specific functional domains, leaving others intact. These lines may also be useful for exploring interactions between hαSYN and environmental or genetic risk factors in dopamine-related disorders using a mouse model.
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影响因子：
6.1
作者：
Chen, Li;Thiruchelvam, Mona J.;Richfield, Eric K.
通讯作者：
Richfield, Eric K.
DOI：
10.1523/jneurosci.1817-09.2009
发表时间：
2009-06-17
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Cartier AE;Djakovic SN;Salehi A;Wilson SM;Masliah E;Patrick GN
通讯作者：
Patrick GN
影响因子：
3.5
作者：
Bönsch, D;Lederer, T;Bleich, S
通讯作者：
Bleich, S
DOI：
10.1111/j.1530-0277.2007.00337.x
发表时间：
2007-04-01
影响因子：
3.2
作者：
Foroud, Tatiana;Wetherill, Leah Flury;Edenberg, Howard J.
通讯作者：
Edenberg, Howard J.
影响因子：
3.3
作者：
Holzmann, C;Krüger, R;Riess, O
通讯作者：
Riess, O