Behavioral Study on the Gracile Axonal Dystrophy (GAD) Mutant Mouse

Yamazaki, Kazuto; Nakazawa, Takahiro; Matsunaga, Manabu; Kumazawa, Akira; Kaneko, Takeru; Wakabayashi, Tsuneo

doi:10.1538/expanim1978.41.4_523

Cited by 3 publications

(1 citation statement)

References 8 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Mice homozygous for the null mutation can be identified as early as 6 weeks of age by the failure to spread their hindlimbs when suspended by the tail (in this and other behavioral assays heterozygous mice are indistinguishable from wild type animals). At various ages the UCHL1 mice have comparable performance on a rotating rod (data not shown) to that reported for GAD mice (Yamazaki et al, 1992). With regard to weight all three genotypes are indistinguishable at 12 weeks of age at which point null mice plateau and are sacrificed when the differential between their weight and healthy littermates reaches 20%.…”

Section: Resultssupporting

confidence: 68%

Loss of UCHL1 promotes age-related degenerative changes in the enteric nervous system

Coulombe

Gamage

Gray

et al. 2014

Front. Aging Neurosci.

View full text Add to dashboard Cite

UCHL1 (ubiquitin carboxyterminal hydrolase 1) is a deubiquitinating enzyme that is particularly abundant in neurons. From studies of a spontaneous mutation arising in a mouse line it is clear that loss of function of UCHL1 generates profound degenerative changes in the central nervous system, and it is likely that a proteolytic deficit contributes to the pathology. Here these effects were found to be recapitulated in mice in which the Uchl1 gene had been inactivated by homologous recombination. In addition to the previously documented neuropathology associated with loss of UCHL1 function, axonal swellings were detected in the striatum. In agreement with previously reported findings the loss of UCHL1 function was accompanied by perturbations in ubiquitin pools, but glutathione levels were also significantly depleted in the brains of the knockout mice, suggesting that oxidative defense mechanisms may be doubly compromised. To determine if, in addition to its role in the central nervous system, UCHL1 function is also required for homeostasis of the enteric nervous system the gastrointestinal tract was analyzed in UCHL1 knockout mice. The mice displayed functional changes and morphological changes in gut neurons that preceded degenerative changes in the brain. The changes were qualitatively and quantitatively similar to those observed in wild type mice of much greater age, and strongly resemble changes reported for elderly humans. UCHL1 knockout mice should therefore serve as a useful model of gut aging.

show abstract

Section: Resultssupporting

confidence: 68%

Loss of UCHL1 promotes age-related degenerative changes in the enteric nervous system

Coulombe

Gamage

Gray

et al. 2014

Front. Aging Neurosci.

View full text Add to dashboard Cite

show abstract

Role of UCHL1 in the pathogenesis of neurodegenerative diseases and brain injury

Mi¹,

Graham²

2023

Ageing Research Reviews

View full text Add to dashboard Cite

Progress in Genetic Studies of Pain and Analgesia

LaCroix-Fralish

Mogil

2009

Annu. Rev. Pharmacol. Toxicol.

157

115

View full text Add to dashboard Cite

Interindividual variability in pain sensitivity and the response to analgesic manipulations remains a considerable clinical challenge as well as an area of intense scientific investigation. Techniques in this field have matured rapidly so that much relevant data have emerged only in the past few years. Our increasing understanding of the genetic mediation of these biological phenomena have nonetheless revealed their surprising complexity. This review provides a comprehensive picture and critical analysis of the field and its prospects.

show abstract

Behavioral Study on the Gracile Axonal Dystrophy (GAD) Mutant Mouse

Cited by 3 publications

References 8 publications

Loss of UCHL1 promotes age-related degenerative changes in the enteric nervous system

Loss of UCHL1 promotes age-related degenerative changes in the enteric nervous system

Role of UCHL1 in the pathogenesis of neurodegenerative diseases and brain injury

Progress in Genetic Studies of Pain and Analgesia

Contact Info

Product

Resources

About