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Genome engineering in cattle: recent technological advancements

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Abstract

Great strides in technological advancements have been made in the past decade in cattle genome engineering. First, the success of cloning cattle by somatic cell nuclear transfer (SCNT) or chromatin transfer (CT) is a significant advancement that has made obsolete the need for using embryonic stem (ES) cells to conduct cell-mediated genome engineering, whereby site-specific genetic modifications can be conducted in bovine somatic cells via DNA homologous recombination (HR) and whereby genetically engineered cattle can subsequently be produced by animal cloning from the genetically modified cells. With this approach, a chosen bovine genomic locus can be precisely modified in somatic cells, such as to knock out (KO) or knock in (KI) a gene via HR, a gene-targeting strategy that had almost exclusively been used in mouse ES cells. Furthermore, by the creative application of embryonic cloning to rejuvenate somatic cells, cattle genome can be sequentially modified in the same line of somatic cells and complex genetic modifications have been achieved in cattle. Very recently, the development of designer nucleases—such as zinc finger nucleases (ZFNs) and transcription activator-like effector nuclease (TALENs), and clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9 (CRISPR/Cas9)—has enabled highly efficient and more facile genome engineering in cattle. Most notably, by employing such designer nucleases, genomes can be engineered at single-nucleotide precision; this process is now often referred to as genome or gene editing. The above achievements are a drastic departure from the traditional methods of creating genetically modified cattle, where foreign DNAs are randomly integrated into the animal genome, most often along with the integrations of bacterial or viral DNAs. Here, I review the most recent technological developments in cattle genome engineering by highlighting some of the major achievements in creating genetically engineered cattle for agricultural and biomedical applications.

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Abbreviations

SCNT:

Somatic cell nuclear transfer

CT:

Chromatin transfer

ES:

Embryonic stem cells

HR:

Homologous recombination

KO:

Knock out

KI:

Knock in

PN:

Pronuclear

CGH:

Comparative genomic hybridization

ZFNs:

Zinc finger nucleases

TALENs:

Transcription activator-like effector nuclease

CRISPR/Cas9:

Clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9

HDR:

Homology-directed repair

NHEJ:

Nonhomologous end joining

PGK:

Phosphoglycerate kinase-1

ST SV40:

Promoter and thymidine kinase enhancer

CAG:

Chicken beta-actin promoter with CMV enhancer

HAC:

Human artificial chromosome

Indel:

Insertion or deletion of DNA base pair(s)

hEPO:

Human erythropoietin

hSA:

Human serum albumin

BSA:

Bovine serum albumin

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  1. Department of Animal, Dairy and Veterinary Sciences, Utah State University of Utah, UMC 9825, 4700 Old Main Hill, Logan, UT, 84322, USA

    Zhongde Wang

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Responsible Editors: Natalay Kouprina and Vladimir Larionov

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Wang, Z. Genome engineering in cattle: recent technological advancements. Chromosome Res 23, 17–29 (2015). https://doi.org/10.1007/s10577-014-9452-6

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