Generation and propagation of high fecundity gene edited fine wool sheep by CRISPR/Cas9
Abstract CRISPR/Cas9 technology has been widely utilized to enhance productive performance, increase disease resistance and generate medical models in livestock. The FecB allele in sheep is a mutation in the BMPRIB gene, recognized as the first major gene responsible for the high fecundity trait in...
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Nature Portfolio
2025-01-01
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| Online Access: | https://doi.org/10.1038/s41598-025-86592-w |
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| author | Xuemei Zhang Meiyu Qiu Bing Han Li Liao Xinrong Peng Jiapeng Lin Ning Zhang Lati Hai Long Liang Yila Ma Wenrong Li Mingjun Liu |
| author_facet | Xuemei Zhang Meiyu Qiu Bing Han Li Liao Xinrong Peng Jiapeng Lin Ning Zhang Lati Hai Long Liang Yila Ma Wenrong Li Mingjun Liu |
| author_sort | Xuemei Zhang |
| collection | DOAJ |
| description | Abstract CRISPR/Cas9 technology has been widely utilized to enhance productive performance, increase disease resistance and generate medical models in livestock. The FecB allele in sheep is a mutation in the BMPRIB gene, recognized as the first major gene responsible for the high fecundity trait in sheep, leading to an increased ovulation rate in ewe. In this study, we employed CRISPR/Cas9-mediated homologous-directed repair (HDR) to introduce a defined point mutation (c.746 A > G) using single-stranded oligonucleotides (ssODN) and the ligase IV inhibitor (SCR7) into the BMPRIB gene of fine wool sheep. A total of nine gene-edited sheep were produced, six of which carried the targeted point mutation, with a precise base substitution efficiency (A > G) of 31.6%. Based on the six targeted founders (F0), we expanded the BMPRIB-targeted population, which included F1 heterozygous (B+) and F2 homozygous(BB) or heterozygous offspring. The average litter size of F1 ewes carrying the B + allele reached 170%, comparable to that of heterozygous native Australian Booroola sheep. Gene-edited ewes with B + and BB genotype produced 0.62 and 0.42 more lambs, respectively, compared to wide-type ewes (p < 0.01). Our results also indicated that the parity signification, our data demonstrate that highly efficient introduction of the intended base mutation into the sheep genome can be achieved by combining the CRISPR/Cas9 system with ssODN and SCR7. The offspring of BMPR/B edited sheep with the defined mutation exhibited high fecundity performance. Compared to conventional sheep breeding strategies, genetic improvement through gene editing offered significant advantages without compromising the fine wool traits of Merino sheep, which are often affected by routine cross-breeding methods. |
| format | Article |
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| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
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| series | Scientific Reports |
| spelling | doaj-art-53098d48364c414f8afdd5dd494e09bf2025-01-26T12:24:21ZengNature PortfolioScientific Reports2045-23222025-01-0115111010.1038/s41598-025-86592-wGeneration and propagation of high fecundity gene edited fine wool sheep by CRISPR/Cas9Xuemei Zhang0Meiyu Qiu1Bing Han2Li Liao3Xinrong Peng4Jiapeng Lin5Ning Zhang6Lati Hai7Long Liang8Yila Ma9Wenrong Li10Mingjun Liu11Key Laboratory of Genetics, Breeding and Reproduction of Grass-Feeding Livestock, Key Laboratory of Animal Biotechnology of Xinjiang, Ministry of Agriculture(MOA)Key Laboratory of Genetics, Breeding and Reproduction of Grass-Feeding Livestock, Key Laboratory of Animal Biotechnology of Xinjiang, Ministry of Agriculture(MOA)Key Laboratory of Genetics, Breeding and Reproduction of Grass-Feeding Livestock, Key Laboratory of Animal Biotechnology of Xinjiang, Ministry of Agriculture(MOA)Key Laboratory of Genetics, Breeding and Reproduction of Grass-Feeding Livestock, Key Laboratory of Animal Biotechnology of Xinjiang, Ministry of Agriculture(MOA)Key Laboratory of Genetics, Breeding and Reproduction of Grass-Feeding Livestock, Key Laboratory of Animal Biotechnology of Xinjiang, Ministry of Agriculture(MOA)Key Laboratory of Genetics, Breeding and Reproduction of Grass-Feeding Livestock, Key Laboratory of Animal Biotechnology of Xinjiang, Ministry of Agriculture(MOA)Key Laboratory of Genetics, Breeding and Reproduction of Grass-Feeding Livestock, Key Laboratory of Animal Biotechnology of Xinjiang, Ministry of Agriculture(MOA)Key Laboratory of Genetics, Breeding and Reproduction of Grass-Feeding Livestock, Key Laboratory of Animal Biotechnology of Xinjiang, Ministry of Agriculture(MOA)Key Laboratory of Genetics, Breeding and Reproduction of Grass-Feeding Livestock, Key Laboratory of Animal Biotechnology of Xinjiang, Ministry of Agriculture(MOA)Key Laboratory of Genetics, Breeding and Reproduction of Grass-Feeding Livestock, Key Laboratory of Animal Biotechnology of Xinjiang, Ministry of Agriculture(MOA)Key Laboratory of Genetics, Breeding and Reproduction of Grass-Feeding Livestock, Key Laboratory of Animal Biotechnology of Xinjiang, Ministry of Agriculture(MOA)Key Laboratory of Genetics, Breeding and Reproduction of Grass-Feeding Livestock, Key Laboratory of Animal Biotechnology of Xinjiang, Ministry of Agriculture(MOA)Abstract CRISPR/Cas9 technology has been widely utilized to enhance productive performance, increase disease resistance and generate medical models in livestock. The FecB allele in sheep is a mutation in the BMPRIB gene, recognized as the first major gene responsible for the high fecundity trait in sheep, leading to an increased ovulation rate in ewe. In this study, we employed CRISPR/Cas9-mediated homologous-directed repair (HDR) to introduce a defined point mutation (c.746 A > G) using single-stranded oligonucleotides (ssODN) and the ligase IV inhibitor (SCR7) into the BMPRIB gene of fine wool sheep. A total of nine gene-edited sheep were produced, six of which carried the targeted point mutation, with a precise base substitution efficiency (A > G) of 31.6%. Based on the six targeted founders (F0), we expanded the BMPRIB-targeted population, which included F1 heterozygous (B+) and F2 homozygous(BB) or heterozygous offspring. The average litter size of F1 ewes carrying the B + allele reached 170%, comparable to that of heterozygous native Australian Booroola sheep. Gene-edited ewes with B + and BB genotype produced 0.62 and 0.42 more lambs, respectively, compared to wide-type ewes (p < 0.01). Our results also indicated that the parity signification, our data demonstrate that highly efficient introduction of the intended base mutation into the sheep genome can be achieved by combining the CRISPR/Cas9 system with ssODN and SCR7. The offspring of BMPR/B edited sheep with the defined mutation exhibited high fecundity performance. Compared to conventional sheep breeding strategies, genetic improvement through gene editing offered significant advantages without compromising the fine wool traits of Merino sheep, which are often affected by routine cross-breeding methods.https://doi.org/10.1038/s41598-025-86592-wBMPRIBCRISPR/Cas 9Fine wool sheepGene edited |
| spellingShingle | Xuemei Zhang Meiyu Qiu Bing Han Li Liao Xinrong Peng Jiapeng Lin Ning Zhang Lati Hai Long Liang Yila Ma Wenrong Li Mingjun Liu Generation and propagation of high fecundity gene edited fine wool sheep by CRISPR/Cas9 Scientific Reports BMPRIB CRISPR/Cas 9 Fine wool sheep Gene edited |
| title | Generation and propagation of high fecundity gene edited fine wool sheep by CRISPR/Cas9 |
| title_full | Generation and propagation of high fecundity gene edited fine wool sheep by CRISPR/Cas9 |
| title_fullStr | Generation and propagation of high fecundity gene edited fine wool sheep by CRISPR/Cas9 |
| title_full_unstemmed | Generation and propagation of high fecundity gene edited fine wool sheep by CRISPR/Cas9 |
| title_short | Generation and propagation of high fecundity gene edited fine wool sheep by CRISPR/Cas9 |
| title_sort | generation and propagation of high fecundity gene edited fine wool sheep by crispr cas9 |
| topic | BMPRIB CRISPR/Cas 9 Fine wool sheep Gene edited |
| url | https://doi.org/10.1038/s41598-025-86592-w |
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