Genetic Modification in Animals: Techniques, Applications, and Ethical Considerations, Slides of Animal Anatomy and Physiology

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Genetic Modification in Animals

Ken Bondioli

Genetic Modification in Animals

“Traditional transgenics”. Insertion of recombinant DNA (a Transgene) into the genome of an animal.

• Germ line transmission
• Random Insertion
• Nuclear injection (early stage embryos)
• Nuclear transfer (Cloning) Genomic editing. Molecular tools to make small changes “editing” in the genome at precise locations.

Incorporation of Transgene as early As possible in Development so all Cells contain the transgene

Characteristics of Transgenic Animals

Low Percentage of animals born are Transgenic Not all Express Transgene

• Random Position Effects Select Founder Animal(s) Establish Line usually from One Animal
• Breeding, Embryo Transfer, Cloning?

Transgenics by Cloning

Transfection of a transgene by Electroporation

• Millions of Cells. Cultured Cells Rare Events Selected for in Culture Cloning Captures Altered Genotype of Cells as an Animal with germ line transmission of the transgene. Allows Precise Changes. Gene Targeting
• Disrupt Gene Function. Gene Knockout.

Commercialization of Transgenic

Animals

One transgenic animal approved for production and sale as food

• Transgenic salmon Transgenic Animals for Biomedical Science
• Most immediate application
• Pharmaceutical product (anti-coagulating protein, anti-thrombin) from milk of a transgenic goat approved in Europe and US
• Numerous models of human disease. Laboratory and domestic animals

Transgenic Animals in Agriculture

New “Improved” Products

Transgenic Animals in Agriculture

New “Improved” Products

• Fat Content and Type. Omega 3 fats
• Anti bacterial proteins in milk. Increased shelf life. Increased resistance to disease in children resulting from contaminated water. Environmental Friendly Animals
• Phytase Pig. Reduced Phosphorus excretion

Molecular Genome Editing

Inducing precise changes in the genome such as deletions or exchanging sequences without introducing a transgene. Zinc Finger Nucleases (ZFN). Transcription Activator-like Effector Nucleases (TALENS). Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)

• CRISPR-associated endonuclease cas

Genome Editing

Prolactin Receptor Genes Slick allele J. Anim. Sci 2017

Gene Editing Regulation

• USDA (plants) In two separate cases (corn and mushrooms) decided not to regulate.
• FDA (animals) recognizes that gene editing does not fit definition of transgenic (legal issue), but has been unsure how to regulate.
• Recently decided in one case to do “risk assessment” and elected not to regulate.
• Unsure how this will translate to other cases.

2022