INVESTIGATING THE POTENTIAL OF X CHROMOSOME SHREDDING FOR MOUSE GENETIC BIOCONTROL

Investigating the potential of X chromosome shredding for mouse genetic biocontrol

Investigating the potential of X chromosome shredding for mouse genetic biocontrol

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Abstract CRISPR-Cas9 technology has facilitated development of strategies that can potentially provide more humane and effective methods to control invasive vertebrate species, such as mice.One promising strategy is X chromosome shredding which aims to bias offspring towards males, resulting in a gradual and unsustainable decline of females.This method has been explored in insects with encouraging results.Here, we investigated this strategy in Mus musculus by targeting repeat DNA sequences on the X chromosome with the aim of inducing sufficient DNA Vintage Collection Carded damage to specifically eliminate X chromosome-bearing sperm during gametogenesis.We tested three different guide RNAs (gRNAs) targeting different repeats on the X chromosome, together with three male germline-specific promoters for inducing Cas9 expression at different stages of spermatogenesis.

A modest bias towards mature Y-bearing sperm was detected in some transgenic males, although this did not translate into significant male-biasing of offspring.Instead, cleavage of the X chromosome during meiosis typically resulted in a spermatogenic block, manifest as small testes volume, empty tubules, low Refrigerated Chef Bases sperm concentration, and sub/infertility.Our study highlights the importance of controlling the timing of CRISPR-Cas9 activity during mammalian spermatogenesis and the sensitivity of spermatocytes to X chromosome disruption.

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