| First Author | Prasad K | Year | 2011 |
| Journal | Eur J Neurosci | Volume | 33 |
| Issue | 4 | Pages | 642-56 |
| PubMed ID | 21272100 | Mgi Jnum | J:174647 |
| Mgi Id | MGI:5140278 | Doi | 10.1111/j.1460-9568.2010.07558.x |
| Citation | Prasad K, et al. (2011) Biochemical and morphological consequences of human alpha-synuclein expression in a mouse alpha-synuclein null background. Eur J Neurosci 33(4):642-56 |
| abstractText | A consensus about the functions of human wild-type or mutated alpha-synuclein (alphaSYN) is lacking. Both forms of alphaSYN 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 alphaSYN (hwalphaSYN) or a doubly mutated (A30P*A53T) alphaSYN (hm(2) alphaSYN) in a C57Bl/6J line spontaneously deleted in mouse alphaSYN (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 with 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 9 months of age. Human alphaSYN was predominantly located in neuronal cell bodies, neurites, synapses, and in intraneuronal/intraneuritic aggregates. The hm(2) alphaSYN transgene resulted in more aggregates and dystrophic neurites than did the hw5 transgene. The hwalphaSYN transgene resulted in higher expression of two striatal proteins, synaptogamin 7 and UCHL1, compared with the levels of the hm(2) alphaSYN transgene. These observations suggest that mutations in alphaSYN may impair specific functional domains, leaving others intact. These lines may be useful for exploring interactions between halphaSYN and environmental or genetic risk factors in dopamine-related disorders using a mouse model. |
