Efficient TALEN-mediated myostatin gene editing in goats

Area of Science:

• Livestock genetics
• Animal biotechnology
• Gene editing technologies

Background:

• Myostatin (MSTN) is a key regulator of skeletal muscle mass.
• Modulating MSTN offers potential for enhancing muscle growth in livestock.
• Goats (Capra hircus) were selected as the model organism for this study.

Purpose of the Study:

• To evaluate the efficacy of transcription activator-like effector nucleases (TALENs) for targeted MSTN gene editing in goats.
• To determine if MSTN gene modification can be achieved without adverse developmental effects.
• To establish a method for producing myostatin-modified goats.

Main Methods:

• Development and application of a specific TALEN pair (MTAL-2) targeting the MSTN gene in goat fibroblasts.
• Generation and screening of 272 monoclonal goat fibroblast cell strains for MSTN mutations (mono- or bi-allelic).
• Somatic cell nuclear transfer using ten selected MSTN-mutated cell strains to produce cloned goats.

Main Results:

• The MTAL-2 TALEN system efficiently introduced mutations at the targeted MSTN locus in goat fibroblasts.
• Three cloned goats with distinct MSTN genotypes (MSTN(-/-), MSTN (+/-), and MSTN (+/+)) were successfully produced.
• The genome editing process did not result in developmental disruptions in the cloned offspring.

Conclusions:

• TALENs-mediated gene editing is a highly effective method for precise modification of the MSTN gene in goats.
• The generated MSTN-mutated somatic cells are suitable for producing site-modified goats.
• This study validates TALENs as a viable tool for creating genetically modified livestock with potential for improved muscle characteristics.