Identification of B6SJL mSOD1(G93A) mouse subgroups with different disease progression rates.
Identification of B6SJL mSOD1(G93A) mouse subgroups with different disease progression rates.
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DOI：
10.1002/cne.23814
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发表时间：
2015-12-15
期刊：
影响因子：
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通讯作者：
Jones KJ
中科院分区：
文献类型：
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作者：
Haulcomb MM;Mesnard-Hoaglin NA;Batka RJ;Meadows RM;Miller WM;Mcmillan KP;Brown TJ;Sanders VM;Jones KJ
Disease progression rates among patients with amyotrophic lateral sclerosis (ALS) vary greatly. While the majority of affected individuals survive three – five years following diagnosis, subgroups undergo a more rapidly progressing form, surviving less than one year, or slower progressing forms surviving for nearly 50 years. Genetic heterogeneity and environmental factors pose significant barriers in investigating patient progression rates. Similar to humans, variation in survival within the mSOD1 mouse has been well-documented, but different progression rates have not been investigated. In the present study, we identified two subgroups of B6SJL mSOD1G93A mice with different disease progression rates; fast (FPG) and slow progression groups (SPG), as evidenced by differences in the rate of motor function decline. In addition, increased disease-associated gene expression within the FPG facial motor nucleus confirmed the presence of a more severe phenotype. We hypothesized that a more severe disease phenotype could be the result of 1) an earlier onset of axonal disconnection with a consistent degeneration rate; or 2) a more severe or accelerated degenerative process. We performed a facial nerve transection axotomy in both mSOD1 subgroups, prior to disease onset, as a method to standardize the axonal disconnection. Instead of leading to comparable gene expression in both subgroups, this standardization did not eliminate the severe phenotype in the FPG facial nucleus, suggesting the FPG phenotype is the result of a more severe or accelerated degenerative process. We theorize that these mSOD1 subgroups may be representative of the rapid and slow disease phenotypes often experienced in ALS.
