A transgenic mouse model of spinocerebellar ataxia type 3 resembling late disease onset and gender-specific instability of CAG repeats

作者：Boy Jana; Schmidt Thorsten^*; Schumann Ulrike; Grasshoff Ute; Unser Samy; Holzmann Carsten; Schmitt Ina; Karl Tim; Laccone Franco; Wolburg Hartwig; Ibrahim Saleh; Riess Olaf

来源：Neurobiology of Disease, 2010, 37(2): 284-293.

DOI：10.1016/j.nbd.2009.08.002

• Spinocerebellar ataxia type 3
• Machado-Joseph disease
• SCA3
• MJD
• Polyglutamine
• Intranuclear inclusion bodies
• Transgenic mouse model
• CAG repeat instability
• Late onset

Spinocerebellar ataxia type 3 (SCA3), or Machado-Joseph disease (MJD), is caused by the expansion of a polyglutamine repeat in the ataxin-3 protein. We generated a mouse model of SCA3 expressing ataxin-3 with 148 CAG repeats under the control of the huntingtin promoter, resulting in ubiquitous expression throughout the whole brain. The model resembles many features of the disease in humans, including a late onset of symptoms and CAG repeat instability in transmission to offspring. We observed a biphasic progression of the disease, with hyperactivity during the first months and decline of motor coordination after about 1 year of age; however, intranuclear aggregates were not visible at this age. Few and small intranuclear aggregates appeared first at the age of 18 months, further supporting the claim that neuronal dysfunction precedes the formation of intranuclear aggregates.

• 出版日期2010-2