Generation of Cynomolgus and Rhesus Monkey Models Carrying the BMPR1BFecB Variant
10.12300/j.issn.1674-5817.2026.122
- VernacularTitle:BMPR1BFecB同源突变的食蟹猴与恒河猴模型构建
- Author:
Chunyang LI
1
;
Xingchen LIU
1
;
Yuzhuo LI
1
;
Yong LU
1
;
Yan WANG
1
;
Changshan GAO
1
;
Yanhong NIE
1
;
Xinyan BIAN
1
;
Chao HU
2
;
Jiaqiao ZHU
2
;
Qiang SUN
1
Author Information
1. Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai 200031, China
2. College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, China
- Publication Type:Journal Article
- Keywords:
Bone morphogenetic protein receptor type 1B;
Base editing;
BMPR1BFecB variant;
Cynomolgus monkey;
Rhesus monkey
- From:
Laboratory Animal and Comparative Medicine
2026;46(4):467-475
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo generate cynomolgus and rhesus monkey models carrying the Booroola fecundity (FecB) variant of bone morphogenetic protein receptor type 1B (BMPR1B) gene (designated BMPR1BFecB) using adenine base edit technology and to explore genetic improvement strategies for enhancing the reproductive performance of laboratory macaques. MethodsFour single-guide RNAs (sgRNAs) were designed to target the BMPR1B c.746A>G locus in cynomolgus and rhesus monkeys. The sgRNAs were combined with the ABE8e-SpRY base editor, and the resulting editing complexes were microinjected into zygotes of both macaque species. Following in vitro culture of the injected embryos, nested PCR amplification was performed to detect the base-editing efficiency at the target site to screen for highly efficient sgRNAs. Subsequently, normally developing gene-edited embryos were transferred into the oviducts of surrogates. Seven days after birth, ear skin or peripheral blood samples were collected from the newborn monkeys for genotyping and mosaicism analysis, and the growth, development, and health status of the gene-edited monkeys were monitored. ResultsAmong the four candidate sgRNAs, sgRNA4 was identified as achieving 100% editing efficiency at the c.746A>G site. A total of 17 live monkey offspring were obtained via embryo transfer, including 8 cynomolgus monkeys and 9 rhesus monkeys. Genotyping results showed that all 8 newborn cynomolgus monkeys carried the c.746A>G point mutation, with an editing efficiency of 100% (8/8), of which 37.50% (3/8) were mosaics. Among the 9 newborn rhesus monkeys, 8 individuals carried the c.746A>G mutation, with an editing efficiency of 88.89% (8/9), of which 75.00% (6/8) were mosaics. ConclusionThe ABE8e-SpRY base-editing system enables precise editing at the c.746A>G (p.Q249R) locus of the BMPR1B gene in both cynomolgus and rhesus monkey embryos, resulting in the successful establishment of laboratory monkey models carrying the BMPR1BFecB variant. These models provide a valuable foundation for future studies of the regulatory role of the BMPR1BFecB variant in reproductive performance at the non‑human primate level, as well as for exploring genetic improvement strategies to enhance reproductive performance in laboratory monkeys.
