ESTABLISHMENT OF A TRANSGENIC MONKEY MODEL OF HUNTINGTON?S DISEASE

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. We have established four transgenic Huntington's disease (HD) monkey founders and four wild-type non-transgenic monkeys for longitudinal evaluation of HD progression. Among these HD monkeys, one (HD9) is 29 months old and carries an Exon 1 of htt gene with 29 CAG repeats under the regulation of a human polyubiquitin-C promoter. The other three HD monkeys (two are seventeen months and one is fifteen months) carry an htt fragment of 512aa with various CAG repeats (HD14: 65; HD16: 29, 57 and 71; and HD17: 70) under the regulation of a human htt promoter. In addition to the four transgenic HD monkeys, we had two male and two female wild-type non-transgenic monkeys serving as controls. They were assigned to the study shortly after birth and have received identical testing and treatment as the HD monkeys, including all cognitive behavioral tests, MRI every six months, monthly blood collection (plasma, serum and lymphocyte bank), and the establishment of lymphoblast cell lines every six months. We recently assigned four adult females and one male for the development of a gamete cryopreservation technique. The objective of the project is to continue monitoring the progression of HD in the HD monkeys and the development of a cryopreservation technique for preserving gametes of HD monkeys, which is important for future expansion of the HD monkey colony and preserving the genetic constitution of the HD monkeys.