Renee R Handley, Suzanne J Reid, Zoe Burch, Jessie C Jacobsen, Tammy Gillis, Kevin Correia, Skye R Rudiger, Clive J McLaughlin, C Simon Bawden, Marcy E MacDonald, Vanessa C Wheeler, Russell G Snell
{"title":"亨廷顿氏症转基因绵羊模型中体细胞 CAG 重复序列的稳定性。","authors":"Renee R Handley, Suzanne J Reid, Zoe Burch, Jessie C Jacobsen, Tammy Gillis, Kevin Correia, Skye R Rudiger, Clive J McLaughlin, C Simon Bawden, Marcy E MacDonald, Vanessa C Wheeler, Russell G Snell","doi":"10.3233/JHD-231516","DOIUrl":null,"url":null,"abstract":"<p><p>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.</p>","PeriodicalId":16042,"journal":{"name":"Journal of Huntington's disease","volume":null,"pages":null},"PeriodicalIF":2.1000,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11091634/pdf/","citationCount":"0","resultStr":"{\"title\":\"Somatic CAG Repeat Stability in a Transgenic Sheep Model of Huntington's Disease.\",\"authors\":\"Renee R Handley, Suzanne J Reid, Zoe Burch, Jessie C Jacobsen, Tammy Gillis, Kevin Correia, Skye R Rudiger, Clive J McLaughlin, C Simon Bawden, Marcy E MacDonald, Vanessa C Wheeler, Russell G Snell\",\"doi\":\"10.3233/JHD-231516\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>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.</p>\",\"PeriodicalId\":16042,\"journal\":{\"name\":\"Journal of Huntington's disease\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":2.1000,\"publicationDate\":\"2024-01-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11091634/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Huntington's disease\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.3233/JHD-231516\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"NEUROSCIENCES\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Huntington's disease","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.3233/JHD-231516","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"NEUROSCIENCES","Score":null,"Total":0}
Somatic CAG Repeat Stability in a Transgenic Sheep Model of Huntington's Disease.
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.
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