Recent advances in gene editing technology have introduced the potential for application of mutagenesis approaches in nonhuman primates to model human development and disease. Here we report successful TALEN-mediated mutagenesis of an X-linked, Rett syndrome (RTT) gene, methyl-CpG binding protein 2 (MECP2), in both rhesus and cynomolgus monkeys. Microinjection of MECP2-targeting TALEN plasmids into rhesus and cynomolgus zygotes leads to effective gene editing of MECP2 with no detected off-target mutagenesis. Male rhesus (2) and cynomolgous (1) fetuses carrying MECP2 mutations in various tissues including testes were miscarried during midgestation, consistent with RTT-linked male embryonic lethality in humans. One live delivery of a female cynomolgus monkey occurred after 162 days of gestation, with abundant MECP2 mutations in peripheral tissues. We conclude that TALEN-mediated mutagenesis can be an effective tool for genetic modeling of human disease in nonhuman primates.
Download full-text PDF |
Source |
---|---|
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4024384 | PMC |
http://dx.doi.org/10.1016/j.stem.2014.01.018 | DOI Listing |
Animal Model Exp Med
January 2025
Institute of Medical Biology Chinese Academy of Medical Sciences Peking Union Medical College Yunnan Key Laboratory of Vaccine Research Development on Severe Infectious Disease Medical Primate Research Center, Chinese Academy of Medical Sciences, Kunming, China.
Background: Non-human primates (NPHs), such as rhesus macaques, cynomolgus monkeys, and Assamese macaques, play a crucial role in biomedical research. However, baseline cytokine and electrolyte data for these three species, particularly data stratified by age and sex, are limited. Therefore, the aim of this study was to establish and analyze age- and sex-specific cytokine and electrolyte profiles in these three species.
View Article and Find Full Text PDFAndrology
December 2024
Contraceptive Development Program, Division of Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institute of Health, Bethesda, Maryland, USA.
Background: Dimethandrolone undecanoate (DMAU) is under development as a single agent hormonal male contraceptive. DMAU is a prodrug hydrolyzed by esterase(s) to the active metabolite dimethandrolone (DMA) which has dual androgenic and progestogenic actions. Phase 1 clinical trial results show DMAU to be well-tolerated as an oral contraceptive in healthy men; however, delivery of DMAU as a long-acting injectable rather than a daily oral formulation would provide user compliance benefits and address oral bioavailability concerns.
View Article and Find Full Text PDFNat Commun
December 2024
State Key Laboratory of Pathogen and Biosecurity, Academy of Military Medical Sciences, Beijing, China.
The recent worldwide outbreaks of mpox prioritize the development of a safe and effective mRNA vaccine. The contemporary mpox virus (MPXV) exhibits changing virological and epidemiological features, notably affecting populations already vulnerable to human immunodeficiency virus (HIV). Herein, we profile the immunogenicity of AR-MPXV5, a penta-component mRNA vaccine targeting five specific proteins (M1R, E8L, A29L, A35R, and B6R) from the representative contemporary MPXV clade II strain, in both naive and simian immunodeficiency virus (SIV)-infected nonhuman primates.
View Article and Find Full Text PDFVet Clin Pathol
December 2024
Wisconsin National Primate Research Center, University of Wisconsin-Madison, Madison, Wisconsin, USA.
Objective: In this study, we aim to determine if machine learning can reduce manual smear review (MSR) rates while meeting or exceeding the performance of traditional MSR criteria.
Method: 9938 automated CBCs with paired MSRs were performed on samples from rhesus and cynomolgus macaques. The definition of a positive (abnormal) smear was determined.
J Vet Diagn Invest
December 2024
California National Primate Center, University of California-Davis, Davis, CA, USA.
Lymphoproliferative disorders of natural killer (NK)-cell lineage are well documented in humans but have yet to be documented in non-human primates (NHPs). Here we describe a case of NK-cell lymphoproliferative disorder/leukemia in a 20-y-old captive female rhesus macaque (). The animal clinically had mild splenomegaly and marked lymphocytosis with small-to-medium lymphocytes in blood smears.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!