Identification of B6SJL mSOD1G93A mouse subgroups with different disease progression rates

التفاصيل البيبلوغرافية
العنوان: Identification of B6SJL mSOD1G93A mouse subgroups with different disease progression rates
المؤلفون: Haulcomb, Melissa M., Mesnard-Hoaglin, Nichole A., Batka, Richard J., Meadows, Rena M., Miller, Whitney M., McMillan, Kathryn P., Brown, Todd J., Sanders, Virginia M., Jones, Kathryn J.
سنة النشر: 2015
مصطلحات موضوعية: Superoxide Dismutase, Amyotrophic Lateral Sclerosis, Motor Disorders, Age Factors, Mice, Transgenic, Feeding Behavior, Laser Capture Microdissection, Transfection, Article, Mice, Inbred C57BL, Disease Models, Animal, Facial Nerve, Mice, Mutation, Sensation Disorders, Disease Progression, Animals, Muscle Strength, RNA, Messenger
الوصف: Disease progression rates among patients with amyotrophic lateral sclerosis (ALS) vary greatly. Although the majority of affected individuals survive 3-5 years following diagnosis, some subgroups experience a more rapidly progressing form, surviving less than 1 year, and other subgroups experience slowly progressing forms, surviving nearly 50 years. Genetic heterogeneity and environmental factors pose significant barriers in investigating patient progression rates. Similar to the case for humans, variation in survival within the mSOD1 mouse has been well documented, but different progression rates have not been investigated. The present study identifies two subgroups of B6SJL mSOD1(G93A) mice with different disease progression rates, a fast progression group (FPG) and slow progression group, 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 hypothesize 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 that the FPG phenotype is the result of a more severe or accelerated degenerative process. We theorize that these mSOD1 subgroups are representative of the rapid and slow disease phenotypes often experienced in ALS.
اللغة: English
URL الوصول: https://explore.openaire.eu/search/publication?articleId=pmid________::6224e0e0e9457b468851341124d071c6
https://europepmc.org/articles/PMC4607568/
Rights: OPEN
رقم الانضمام: edsair.pmid..........6224e0e0e9457b468851341124d071c6
قاعدة البيانات: OpenAIRE