BRC Current Technology June 2022

RIKEN BRC BRC Current Technology
June 2022

18. Successful increase of the litter size
in mice by 1.4 times

Development of pregnancy-safe
anti-inhibin monoclonal antibodies

(a)(b)(c)(d)(e)

(a) Schematic representation of superovulation using anti-inhibin monoclonal antibody (AIMA) and mating. (b) AIMA treatment significantly increases the litter sizes 1.4-fold in C57BL/6J and ICR mice. (c) Genome editing (i-GONAD) for tyrosinase with AIMA treatment increases the number of pups. (d) Ten out of 12 pups had non-pigmented eyes, as expected. (e) Gene-edited albino C57BL/6J pups from an i-GONAD-treated female after AIMA injection. *P < 0.05

In mammals, the number of offspring produced by a female is determined by follicle-stimulating hormone (FSH) that supports oocyte growth and other reproductive factors in each species. We produced anti-inhibin monoclonal antibodies (AIMAs) to block inhibin, which suppresses FSH secretion, and successfully increased the litter sizes by administering it [1]. The litter sizes increased approximately 1.4-fold in C57BL/6J and ICR mice, and the resultant offspring grew normally. We applied this technique to the in vivo-genome editing method (i-GONAD) [2], and attained an 1.5-fold increase in the number of pups after i-GONAD treatment without affecting the genome-editing efficiency (in collaboration with Prof. M. Ohtsuka, Tokai University) [1].
 This AIMA technique method may be effective in improving reproductive performance of mouse strains, especially in the cases of using aged females, genome editing by i-GONAD, and propagation of mouse strains with poor reproductive ability.

 

References: [1] A Hasegawa et al., “Use of anti-inhibin monoclonal antibody for increasing the litter size of mouse strains and its application to in vivo-genome editing technology,”
Biol. Reprod. 2022 Apr 2:ioac068. doi: 10.1093/biolre/ioac068.
[2] M. Ohtsuka et al., “i-GONAD: a robust method for in situ germline genome engineering using CRISPR nucleases,”
Genome Biol. 2018 Feb 26;19(1):25. doi: 10.1186/s13059-018-1400-x.


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