Somatic CAG Repeat Stability in a Transgenic Sheep Model of Huntington’s Disease-Reference-Cited by-同舟云学术

Somatic CAG Repeat Stability in a Transgenic Sheep Model of Huntington’s Disease

Published:2024-03-29 Issue:1 Volume:13 Page:33-40
ISSN:1879-6397
Container-title:Journal of Huntington's Disease
language:
Short-container-title:JHD

Author:

Handley Renee R.¹,Reid Suzanne J.¹,Burch Zoe²,Jacobsen Jessie C.¹,Gillis Tammy²,Correia Kevin²,Rudiger Skye R.³,McLaughlin Clive J.³,Bawden C. Simon³,MacDonald Marcy E.²⁴,Wheeler Vanessa C.²⁴,Snell Russell G.¹

Affiliation:

1. Centre for Brain Research, School of Biological Sciences, The University of Auckland, Auckland, New Zealand

2. Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA

3. Molecular Biology and Reproductive Technology, Laboratories, South Australian Research and Development Institute, Adelaide, SA, Australia

4. Department of Neurology, Harvard Medical School, Boston, MA, USA

Abstract

Somatic instability of the huntingtin (HTT) CAG repeat mutation modifies age-at-onset of Huntington’s disease (HD). Understanding the mechanism and pathogenic consequences of instability may reveal therapeutic targets. Using small-pool PCR we analyzed CAG instability in the OVT73 sheep model which expresses a full-length human cDNA HTT transgene. Analyses of five- and ten-year old sheep revealed the transgene (CAG)69 repeat was remarkably stable in liver, striatum, and other brain tissues. As OVT73 sheep at ten years old have minimal cell death and behavioral changes, our findings support instability of the HTT expanded-CAG repeat as being required for the progression of HD.

Publisher

IOS Press

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