Rey Garcia, Anna

Universitat Autònoma de Barcelona. Facultat de Veterinària

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Anna Rey Garcia June 2017INTRODUCTION AND OBJECTIVESCONTROVERSY AND LEGISLATIONThe initial application of the genetically modified animals was to contribute in the basicresearch with the aim to study the function mechanisms of the organism and to achieve abetter understanding of genes function.A transgenic animal is one that has been genetically modified either through the insertionof exogenous genes, or from the elimination or modification of their own genes. The goal isto modify existing features or to add new ones.The target of this review is to show the main applications of genetically modified animals. On the other hand, a second aim is to show the controversy generated by the use of these animals as well as the legislation that is responsible for its regulation.GENETICALLY ENGINEERED LIVESTOCK: APPLICATIONS IN FOOD PRODUCTION AND MEDICINEOriginally, transgenic mammals were created through a technique called pronuclearmicroinjection.The lack of efficiency of this technique has given place to research of new methods toobtain transgenic animals such as retroviral vectors or somatic cell nuclear transfer (SCNT).Recent advances in genome editing have allowed the creation of designer engineerednucleases like ZFN, TALEN and CRISPR/Cas9. These nucleases allow a precise genomeediting in livestock. Its mechanism of action is based on the creation of a double-strandedbreak in the DNA with the aim to stimulate the DNA repair pathway.Figure 1. Structure of ZFN, TALEN and CRISPR/Cas9.        From: Garcia i Pujol (2015)Models of diseaseDisease resistanceEnvironmentGrowth and yieldLivestock have been proposed to overcome the limitations of mice as models of diseasebecause they share anatomical and physiological characteristics with humans. However,they have some limitations, such as production cost or time to be invested to developsimilar diseases to those of humans.• Sheep as models of diseasesof the respiratory system(ex: asthma, cystic fibrosis)• Pigs as models of cardiovasculardiseases (ex. Atherosclerosis)Pigs as models of neurodegenerativediseases (ex. Alzheimer)• Goats have beenused in researchon cystic fibrosis To solve a problem of animal welfare To prevent the spread of zoonotic diseases To reduce the use of antibioticsWhy?Studies: Calves more resistant to mastitisLiu et al. (2013) Liu et al. (2014)Worked with lisostafina (enzyme with antibacterial activity)Worked with human lysozyme (antimicrobial protein)Integration through ZFNickases Integration through ZFN Target gene: β-casein locus Target gene: β-casein locus Figure 4. Transgenic lamb with muscular hypertrophy.              From: Proudfoot et al. (2015)Figure 3. Calves with MSTN biallelic mutations displayed the doubled-muscled phenotype.              From: Luo et al. (2014)Figure 5. Note that MSTN−/− pigs show wider back, fuller rump and thicker limbs.     From: Qian et al. (2015)Figure 6. Differences in growth between AquAdvantage Salmon and conventional during the first three years of life.  From: AquaBounty TechnologiesIn order to increase production many studies have beenconducted to achieve an increase in muscle mass. Somestudies have been working with the gene MSTN, whichencodes for the miostatina, a protein that plays animportant inhibitory role during muscle development.Studies Species TechniqueLuo et al (2014) Cattle ZFNZhao et al. (2016)Sheep TALENProudfoot et al. (2015)Sheep and cattle TALENQian et al. (2015) Pig ZFN Moreover, AquaBounty Technologies createda transgenic salmon that grows twice as bigand at a greater speed than conventionalones.MSTN -/-MSTN -/-CONCLUSIONSControversyAPPLICATIONS OF GENETICALLY ENGINEERED LIVESTOCKPros Cons Improve animal health Public resistance to GE technologyReduce the use of antibiotics Perceived lack of safety infood from GE animals Decreased environmental impact of farmingThreat to the environment (introduction of modified genes into wild populations)LegislationThe EU has established a legal framework to ensure the protection ofhuman and animal health as well as the environment.Regulation of evaluation and authorization of genetically modified foodis determined by:- Directive 2001/18 / EC- Regulation (EC) Nº 1829/2003- Regulation 503/2013 The techniques to obtain genetically modified animals have advanced greatly in recent years. Thanks to the development of nucleases design, we can today mimic natural mutations by placing specificmodifications in the genome. Many studies aim to produce transgenic animals for human consumption. However, most of these animals areonly under investigation at present. Only AquAdvantage salmon has currently been approved for human consumption. Despite the advantages that genetically modified animals could pose, these studies can not come to everydayuse until public opinion is not favourable.METHODS OF MAKING TRANSGENIC ANIMALSGlobal animal phosphorus pollution is aserious and growing problem.Monogastric animals can not digestphytate plant, so they required dietarysupplementation with mineral phosphate.StudyGolovan et al. (2001) have developed thephytase transgenic pig. The saliva of thesepigs contains phytase, which allows acomplete digestion of dietary phytate.Figure 2. Phytase transgenic pig.                               From: http://www.uoguelph.ca/enviropig/

Genetically engineered livestock : applications in food production and medicine

https://ddd.uab.cat/pub/tfg/2017/179924/TFG_areygarcia_poster.pdf

Genetically engineered livestock : applications in food production and medicine

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