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Author Notes:

Correspondence to: Anthony W. S. Chan, Yerkes National Primate Research Center, Ry is supported by a grant awarded by the ORIP/NIH (RR018827) to AWSC.m 2212, Neuroscience Research Bldg., 954 Gatewood Rd. N.E., Atlanta, GA 30329, USA, Email: awchan@emory.edu

SM: preparation of semen for in vitro fertilization, artificial insemination, development and assistance in artificial insemination, infant and general animal care, preparation of samples for molecular analyses, sperm analysis and preparation of manuscript.

TC: preparation of semen for in vitro fertilization and artificial insemination, development and assistance in artificial insemination, infant and general animal care and preparation of samples for molecular analyses.

MSP: genotyping, gene expression analysis and preparation of manuscript.

KA: Derivation and characterization of ESCs and iPSCs. FCS, SJ and KG: development and performance of the artificial insemination technique.

ASWC: experimental design and coordination, data analysis, development of and assistance with artificial insemination, wrote and prepared manuscript and final approval.

All animal procedures and experiments were performed in a BSL-2 facility at the Yerkes National Primate Research Center (YNPRC) and were approved by the Emory University Institutional Animal Care and Use Committee (IACUC).

Yerkes National Primate Research Center is a fully AAALAC-accredited facility. All animals in the colony are managed in accordance with the applicable USDA Animal Welfare Regulations and the Guide for the Care and Use of Laboratory Animals.

We thank Yerkes National Primate Research Center (YNPRC) veterinarians and animal care staff for providing outstanding services, and Ms. Cheryl Timms Strauss at the Department of Human Genetics for editorial assistance.

We also thank members of the Chan laboratory who provided assistance at the nursery and infant care.

Authors have no competing financial interests.

Subjects:

Research Funding:

We also thank members of the Chan laboratory who provided assistance at the nursery and infant care. YNPRC is supported by the National Center for Research Resources P51RR165 and is currently supported by the Office of Research and Infrastructure Program (ORIP)/OD P51OD11132.

This study is supported by a grant awarded by the ORIP/NIH (RR018827) to AWSC.

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Reproductive Biology
  • Veterinary Sciences
  • Transgenic Huntington's disease monkey
  • Germline transmission
  • Second generation
  • Ultrasound-guided intrauterine insemination
  • PLURIPOTENT STEM-CELLS
  • CELLULAR PHENOTYPES
  • REPEAT INSTABILITY
  • NONHUMAN PRIMATE
  • ANIMAL-MODEL
  • GENERATION

Germline transmission in transgenic Huntington's disease monkeys

Tools:

Journal Title:

Theriogenology

Volume:

Volume 84, Number 2

Publisher:

, Pages 277-285

Type of Work:

Article | Post-print: After Peer Review

Abstract:

Transgenic nonhuman primate models are an increasingly popular model for neurologic and neurodegenerative disease because their brain functions and neural anatomies closely resemble those of humans. Transgenic Huntington's disease monkeys (HD monkeys) developed clinical features similar to those seen in HD patients, making the monkeys suitable for a preclinical study of HD. However, until HD monkey colonies can be readily expanded, their use in preclinical studies will be limited. In the present study, we confirmed germline transmission of the mutant huntingtin (mHTT) transgene in both embryonic stem cells generated from three male HD monkey founders (F0) and in second-generation offspring (F1) produced via artificial insemination by using intrauterine insemination technique. A total of five offspring were produced from 15 females that were inseminated by intrauterine insemination using semen collected from the three HD founders (5 of 15, 33%). Thus far, sperm collected from the HD founder (rHD8) has led to two F1 transgenic HD monkeys with germline transmission rate at 100% (2 of 2). mHTT expression was confirmed by quantitative real-time polymerase chain reaction using skin fibroblasts from the F1 HD monkeys and induced pluripotent stem cells established from one of the F1 HD monkeys (rHD8-2). Here, we report the stable germline transmission and expression of the mHTT transgene in HD monkeys, which suggest possible expansion of HD monkey colonies for preclinical and biomedical research studies.

Copyright information:

© 2015 Elsevier Inc.

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