Production of light-coloured, low heat-absorbing Holstein Friesian cattle by precise embryo-mediated genome editing

Jingwei Wei; Brigid Brophy; Sally-Ann Cole; Shane Leath; Björn Oback; Jens Boch; David N. Wells; Götz Laible

doi:10.1071/RD23163

REVIEW (Open Access)

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Production of light-coloured, low heat-absorbing Holstein Friesian cattle by precise embryo-mediated genome editing

Jingwei Wei

^A , Brigid Brophy ^A , Sally-Ann Cole ^A , Shane Leath ^A , Björn Oback ^A ^B ^C , Jens Boch ^D , David N. Wells ^A and Götz Laible ^A ^C ^*

+ Author Affiliations

- Author Affiliations

^A Animal Biotechnology, Ruakura Research Centre, AgResearch, Hamilton, New Zealand.

^B School of Sciences, University of Waikato, Hamilton, New Zealand.

^C Department of Molecular Medicine and Pathology, School of Medical Sciences, University of Auckland, Auckland, New Zealand.

^D Institute of Plant Genetics, Leibniz Universität Hannover, Hannover, Germany.

^* Correspondence to: goetz.laible@agresearch.co.nz

Reproduction, Fertility and Development 36(2) 112-123 https://doi.org/10.1071/RD23163

© 2024 The Author(s) (or their employer(s)). Published by CSIRO Publishing on behalf of the IETS. This is an open access article distributed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND)

Abstract

Context

Genome editing enables the introduction of beneficial sequence variants into the genomes of animals with high genetic merit in a single generation. This can be achieved by introducing variants into primary cells followed by producing a live animal from these cells by somatic cell nuclear transfer cloning. The latter step is associated with low efficiencies and developmental problems due to incorrect reprogramming of the donor cells, causing animal welfare concerns. Direct editing of fertilised one-cell embryos could circumvent this issue and might better integrate with genetic improvement strategies implemented by the industry.

Methods

In vitro fertilised zygotes were injected with TALEN editors and repair template to introduce a known coat colour dilution mutation in the PMEL gene. Embryo biopsies of injected embryos were screened by polymerase chain reaction and sequencing for intended biallelic edits before transferring verified embryos into recipients for development to term. Calves were genotyped and their coats scanned with visible and hyperspectral cameras to assess thermal energy absorption.

Key results

Multiple non-mosaic calves with precision edited genotypes were produced, including calves from high genetic merit parents. Compared to controls, the edited calves showed a strong coat colour dilution which was associated with lower thermal energy absorbance.

Conclusions

Although biopsy screening was not absolutely accurate, non-mosaic, precisely edited calves can be readily produced by embryo-mediated editing. The lighter coat colouring caused by the PMEL mutation can lower radiative heat gain which might help to reduce heat stress.

Implications

The study validates putative causative sequence variants to rapidly adapt grazing cattle to changing environmental conditions.

Keywords: cattle, coat color dilution, embryo-mediated, genome editing, heat stress, homology-directed repair, microinjection, P. Leu18del, PMEL, pre-melanosome protein 17, TALEN.

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