Progressive Polyglutamine Repeat Expansion in Peripheral Blood Cells and Sperm of Transgenic Huntington's Disease Monkeys

J Huntingtons Dis. 2019;8(4):443-448. doi: 10.3233/JHD-190359.

Abstract

The expanded CAG repeat results in somatic mosaicism and genetic anticipation in Huntington's disease (HD). Here we report a longitudinal study examining CAG repeat instability in lymphocytes and sperm of three HD monkeys throughout their whole life-span that encompass the prodromal to symptomatic stages of HD. We demonstrate a progressive increase in CAG repeat length in lymphocytes and sperm as the animals aged. We also examined the impact of CAG repeat length on expansion rate, which showed a clear linear correlation up to 62Q, and high instability after. Our findings stress the importance of further investigation in CAG instability in peripheral blood cells longitudinally.

Keywords: CAG instability; HD monkey; longitudinal; peripheral blood; sperm.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Age Factors
  • Animals
  • Animals, Genetically Modified
  • Disease Models, Animal
  • Genomic Instability / genetics*
  • Haplorhini
  • Huntington Disease / blood
  • Huntington Disease / genetics*
  • Huntington Disease / metabolism*
  • Longitudinal Studies
  • Lymphocytes / metabolism*
  • Male
  • Peptides / genetics
  • Peptides / metabolism*
  • Prodromal Symptoms
  • Spermatozoa / metabolism*
  • Trinucleotide Repeat Expansion / genetics*

Substances

  • Peptides
  • polyglutamine