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Table 1. Publications using gene editing in cattle for agricultural applications, grouped by category of genetic improvement goals.

From: Synergistic power of genomic selection, assisted reproductive technologies, and gene editing to drive genetic improvement of cattle

Goal

Genome target and function

Editing approach

Editora

Live edited offspring

Reference(s)

Animal health/welfare

Prevent horn growth

Horn/Poll

Replaced bovine horned allele (p) with bovine POLLED, Celtic allele (PC)

TALEN

Yes

Carlson et al. (2016), Tan et al. (2013)

Generated deletions in the horned loci

CRISPR/Cas9

No

Hennig et al. (2021a, b)

Disease resistance: Mastitis

CSN2 (Beta-Casein): milk protein gene

Inserted Staphylococcal lysostaphin (antimicrobial) gene

ZFN

Yes

Liu et al. (2013)

Inserted human lysozyme (antimicrobial) gene

ZFN

Yes

Liu et al. (2014)

Disease resistance: Tuberculosis

ITGB2 Intergenic region between SFTPA1 (Surfactant Protein A1) and  MAT1A (Methionine Adenosyltransferase 1A)

Inserted mouse Sp110 (SP110 Nuclear Body Protein) gene

TALEN

Yes

Wu et al. (2015)

Intergenic region between  FSCN1 (Fascin Actin-Bundling Protein 1) and ACTB (Actin Beta)

Inserted human NRAMP1 (Natural Resistance-Associated Macrophage Protein 1) gene (controls Tuberculosis infections)

CRISPR/Cas9

Yes

Gao et al. (2017)

Disease resistance: BRD

(Integrin Subunit Beta 2): encodes the leukocyte signal peptide CD18

Substituted glycine in place of glutamine to cause cleavage of CD18

ZFN

No

Shanthalingam et al. (2016)

Disease resistance: BSE

PRNP (Prion Protein): susceptibility to BSE

Disrupted the PRNP gene

TALEN

No

Choi et al. (2015)

CRISPR/Cas9

No

Bevacqua et al. (2016)

Substituted valine in place of glycine at position 127 to confer resistance

CRISPR/Cas9

Yes

Park et al. (2020)

Repair mutation: IARS syndrome

IARS

Substituted a single base pair to correct the mutation

CRISPR/Cas9

Yes

Ikeda et al. (2017), Ishino et al. (2018)

Thermo tolerance

PMEL (Premelanosomal Protein): coat color

Introduced a 3 bp deletion associated with diluted, or silver, coat-color

CRISPR/Cas9

Yes

Laible et al. (2020)

PRLR (Prolactin Receptor): hair coat length

Disrupted PRLR gene to generate a SLICK (short, sleek hair coat) phenotype

CRISPR/Cas9

Yes

Rodriguez-Villamil et al. (2021)

Product yield or quality

Eliminate a milk allergen

BLG (Beta-Lactoglobulin): whey protein gene

Disrupted the BLG gene

ZFN

Yes

Yu et al. (2011)

Disrupted the BLG gene by inserting 5 bp with single stranded oligonucleotide template

ZFN or TALEN

No

Wei et al. (2015)

TALEN

Yes

Wei et al. (2018)

CSN2: milk protein gene

Inserted LacS gene (sulfolobus solfataricus beta-glycosidase) to digest lactose

TALEN

Yes

Su et al. (2018)

Increase lean muscle yield

MSTN (Myostatin): negative regulator of muscle growth

Disrupted the MSTN gene

TALEN

No

Carlson et al. (2012)

ZFN

Yes

Luo et al. (2014)

TALEN

Yes

Proudfoot et al. (2015)

CRISPR/Cas9

No

Namula et al. (2019)

Reproduction and novel breeding schemes

Generate host for germ cell transfer

NANOS2 (Nanos C2HC-Type Zinc Finger 2): necessary for male germline development

Disrupted the NANOS2 gene to eliminate germ cell production

CRISPR/Cas9

Yes

Ciccarelli et al. (2020), Miao et al. (2019)

Increased frequency of male offspring

Safe harbor loci, H11

Inserted an additional copy of the bovine SRY (Sex Determining Region Y protein) gene

CRISPR/Cas9

Yes

Owen et al. (2021)

  1. aEditor: zinc finger nucleases (ZFN), transcription activator-like effector nucleases (TALENs), and clustered regularly interspersed short palindromic repeats (CRISPR)-associated protein 9 (Cas9). Note: BRD, bovine respiratory disease; BSE, bovine spongiform encephalopathy; IARS, Isoleucyl-tRNA synthetase