Chromosome Research

, Volume 23, Issue 1, pp 17–29

Genome engineering in cattle: recent technological advancements

Review

DOI: 10.1007/s10577-014-9452-6

Cite this article as:
Wang, Z. Chromosome Res (2015) 23: 17. doi:10.1007/s10577-014-9452-6

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.

Keywords

Cattle Genome engineering Genetic modification ZFN TALEN CRISPR/Cas9 

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

Copyright information

© Springer Science+Business Media Dordrecht 2014

Authors and Affiliations

  1. 1.Department of Animal, Dairy and Veterinary SciencesUtah State University of UtahLoganUSA

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