Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
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Query: UMLS:C0085632 (
apathy
)
4,089
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Perry syndrome is a rare neurodegenerative disease characterized by parkinsonism, depression/
apathy
, weight loss, and central hypoventilation. Our previously-conducted genome-wide association scan and subsequent studies identified nine mutations in DCTN1, the largest protein subunit of the dynactin complex, in patients with Perry syndrome. These included G71A in the microtubule-binding cytoskeleton-associated protein Gly-rich domain of
p150
Glued
. The dynactin complex is essential for function of the microtubule-based cytoplasmic retrograde motor dynein. To test the hypothesis that the G71A mutation in the DCTN1 gene is sufficient to cause Perry syndrome, we generated DCTN1
G71A
transgenic mice. These mice initially developed normally, but young animals showed decreased exploratory activity and aged animals showed impaired motor coordination. These behavioral defects parallel
apathy
-like symptoms and parkinsonism encountered in Perry syndrome. TDP-43 aggregates were not detected in the substantia nigra and cerebral cortex of the transgenic mice, although pathological aggregates of TDP-43 have been considered a major neuropathological feature of Perry syndrome. Our study reveals that a single mutation in the DCTN1 gene recapitulates symptoms of Perry syndrome patients, and provides evidence that DCTN1
G71A
transgenic mice represent a novel rodent model of Perry syndrome.
...
PMID:Behavioral defects in a DCTN1
G71A
transgenic mouse model of Perry syndrome. 2927 99
