Germline transmission in transgenic Huntington's disease monkeys.
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.
Department of Human Genetics, Emory University School of Medicine, Atlanta, Georgia, USA; Division of Neuropharmacology and Neurologic Diseases, Yerkes National Primate Research Center, Emory University, Atlanta, Georgia, USA.
Sean
S
Moran
Department of Human Genetics, Emory University School of Medicine, Atlanta, Georgia, USA; Division of Neuropharmacology and Neurologic Diseases, Yerkes National Primate Research Center, Emory University, Atlanta, Georgia, USA.
Tim
T
Chi
Department of Human Genetics, Emory University School of Medicine, Atlanta, Georgia, USA; Division of Neuropharmacology and Neurologic Diseases, Yerkes National Primate Research Center, Emory University, Atlanta, Georgia, USA.
Melinda S
MS
Prucha
Department of Human Genetics, Emory University School of Medicine, Atlanta, Georgia, USA; Division of Neuropharmacology and Neurologic Diseases, Yerkes National Primate Research Center, Emory University, Atlanta, Georgia, USA.
Kwang Sung
KS
Ahn
Division of Animal Resources, Yerkes National Primate Research Center, Emory University, Atlanta, Georgia, USA.
Fawn
F
Connor-Stroud
Division of Animal Resources, Yerkes National Primate Research Center, Emory University, Atlanta, Georgia, USA.
Sherrie
S
Jean
Division of Animal Resources, Yerkes National Primate Research Center, Emory University, Atlanta, Georgia, USA.
Kenneth
K
Gould
Department of Human Genetics, Emory University School of Medicine, Atlanta, Georgia, USA; Division of Neuropharmacology and Neurologic Diseases, Yerkes National Primate Research Center, Emory University, Atlanta, Georgia, USA. Electronic address: awchan@emory.edu.
Anthony W S
AW
Chan
D000818:Animals; D030801:Animals, Genetically Modified; D002454:Cell Differentiation; D004195:Disease Models, Animal; D053595:Embryonic Stem Cells; D005260:Female; D005838:Genotype; D005854:Germ Cells; D000071058:Huntingtin Protein; D006816:Huntington Disease / Q000235:genetics*; D057026:Induced Pluripotent Stem Cells; D007315:Insemination, Artificial / Q000379:methods / Q000662:veterinary; D008253:Macaca mulatta; D008297:Male; D009419:Nerve Tissue Proteins / Q000235:genetics; D009474:Neurons; D039904:Pluripotent Stem Cells; D011247:Pregnancy; D013094:Spermatozoa; D019076:Transgenes / Q000235:genetics
C086055:HTT protein, human; D000071058:Huntingtin Protein; D009419:Nerve Tissue Proteins
Germline transmission; Second generation; Transgenic Huntington's disease monkey; Ultrasound-guided intrauterine insemination