CRISPR-Cas9 effectors facilitate generation of single-sex litters and sex-specific phenotypes

Douglas C
The Francis Crick Institute
January 1, 2021
Nat Commun
https://pubmed.ncbi.nlm.nih.gov/34862376

This article is currently being updated. View its version on PubMed.

https://pubmed.ncbi.nlm.nih.gov/34862376

Research summary

A bicomponent CRISPR‑Cas9 system induces sex-specific embryonic lethality via targeting Top1, enabling generation of all-male or all-female litters with 100% efficiency and litter size compensation. The system can also generate postnatal sex-specific phenotypes.

Key outcome of the study

Co‑inheritance leads to elimination of male or female embryos depending on Cas9‑chromosome; 100% single‑sex litters; litter sizes exceed 50% of controls; system repurposable for sex‑specific phenotypes

Model

Top1 sgRNA Knockin (autosomal H11 locus) combined with Cas9 Knockin (X‑ or Y‑linked) — genOway-developed bicomponent CRISPR‑Cas9 Knockin mouse system

TARGET:
Top1
Synonyms:
Topoisomerase I

Keywords

Genetic sex selection; 3Rs reduction of animal use; synthetic lethality; sex‑specific gene editing; developmental biology

Technical specifications

Synthetic lethal bicomponent CRISPR‑Cas9 system; IRES‑mCherry reporter; autosomal H11‑Top1 sgRNA Knockin; X‑Cas9 or Y‑Cas9 Knockin; embryonic lethality; fluorescent tracking; breeding strategy

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