DOI: 10.1002/ame2.70002
A new CRISPR-mediated Apc knockout allele leads to pyloric gland adenoma-like gastric polyps in mice with C57BL/6;FVB/N mixed background
Sarp Uzun1
Özge Özcan2
Ayşenur Gök2
Aynur Işık3
Sinem Bakır3
Ayşen Günel-Özcan2
İlyas Onbaşılar3
Aytekin Akyol4
1.Hacettepe University Transgenic Animal Technologies Research and Application Center,Ankara,Turkey;Institute of Medical Genetics and Pathology,University Hospital Basel,Basel,Switzerland2.Department of Stem Cell Sciences,Hacettepe University Graduate School of Health Sciences,Ankara,Turkey3.Hacettepe University Transgenic Animal Technologies Research and Application Center,Ankara,Turkey4.Hacettepe University Transgenic Animal Technologies Research and Application Center,Ankara,Turkey;Department of Pathology,Hacettepe University Faculty of Medicine,Ankara,Turkey;Tumor Pathology Division,Hacettepe University Cancer Institute,Ankara,Turkey;Hacettepe University Molecular Pathology Research and Application Center,Ankara,Turkey
摘要：Adenomatous polyposis coli(APC)mutations are the most frequently identified genetic alteration in sporadic colorectal cancer(CRC)cases,and a myriad of genetically engineered Apc-mutant CRC mouse models have been developed using various genetic manipulation techniques.The advent of the CRISPR/Cas9 system has revolutionized the field of genetic engineering and facilitated the development of new genetically engineered mouse models.In this study,we aimed to develop a novel Apc knockout allele using the CRISPR/Cas9 system and evaluate the phenotypic effects of this new allele in two different mouse strains.For this purpose,exon 16 of mouse Apc gene was targeted with a single-guide RNA,and the mouse carrying an Apc frameshift mutation at codon 750(Δ750)was chosen as the founder.The mutant FVB-ApcΔ750 mice were backcrossed with wild-type C57BL/6 mice,and the phenotypic effects of the knockout allele were evaluated in F8-FVB-ApcΔ750,F4-B6;FVB-ApcΔ750,and F1-B6;FVB-ApcΔ750 by a macroscopic and microscopic examination of the gastrointestinal system.The result showed that the mean polyp number was significantly higher in F4-BL6;FVB-ApcΔ750 than in F8-FVB-ApcΔ750.Intestinal polyposis was more prominent in F4-BL6;FVB-ApcΔ750,whereas a higher number of colon polyps than intestinal polyps were observed in F8-FVB-ApcΔ750.Additionally,F1-BL6;FVB-ApcΔ750 mixed background mice developed gastric polyps that morphologically resembled the pyloric gland adenoma of humans.In conclusion,we developed a novel CRISPR-mediated Apc knockout allele using two mouse strains.We showed that this allele can exert a strain-specific effect on the phenotype of mice and can cause gastric polyp formation.
机标关键词：knockoutmixedmicewithadenoma-likeallelebackgroundcrispr-mediated
论文发表日期：2025-03-01
在线出版日期：2025-08-15（本平台首次上网日期，不代表文献的发表时间）
页数：8( 922-929 )
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