Construction of stable mouse artificial chromosome from native mouse chromosome 10 for generation of transchromosomic mice

• Published in: Scientific reports Vol. 11; no. 1; pp. 20050 - 12
• Main Authors: Abe, Satoshi, Honma, Kazuhisa, Okada, Akane, Kazuki, Kanako, Tanaka, Hiroshi, Endo, Takeshi, Morimoto, Kayoko, Moriwaki, Takashi, Hamamichi, Shusei, Nakayama, Yuji, Suzuki, Teruhiko, Takehara, Shoko, Oshimura, Mitsuo, Kazuki, Yasuhiro
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 08-10-2021; Nature Publishing Group; Nature Portfolio
• Subjects: 631/1647/1511; 631/1647/1513; 631/1647/2300; 631/1647/334; 631/208/1405; 631/208/212; 631/61/17; 631/61/212; 631/61/2300; 631/80/103; Animal models; Animals; Artificial chromosomes; Centromere; Centromeres; Chromosome 10; Chromosome 11; Chromosomes; Chromosomes - genetics; Chromosomes, Artificial; Embryonic Stem Cells - cytology; Embryonic Stem Cells - metabolism; Female; Gene Transfer Techniques; Genetic Engineering - methods; Genetic Vectors - genetics; Germ Cells; Humanities and Social Sciences; Male; Medical research; Mice; Mice, Inbred ICR; multidisciplinary; Pharmacokinetics; R&D; Recombination, Genetic; Research & development; Science; Science (multidisciplinary); Zebrafish
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-021-99535-y

Mammalian artificial chromosomes derived from native chromosomes have been applied to biomedical research and development by generating cell sources and transchromosomic (Tc) animals. Human artificial chromosome (HAC) is a precedent chromosomal vector which achieved generation of valuable humanized animal models for fully human antibody production and human pharmacokinetics. While humanized Tc animals created by HAC vector have attained significant contributions, there was a potential issue to be addressed regarding stability in mouse tissues, especially highly proliferating hematopoietic cells. Mouse artificial chromosome (MAC) vectors derived from native mouse chromosome 11 demonstrated improved stability, and they were utilized for humanized Tc mouse production as a standard vector. In mouse, however, stability of MAC vector derived from native mouse chromosome other than mouse chromosome 11 remains to be evaluated. To clarify the potential of mouse centromeres in the additional chromosomes, we constructed a new MAC vector from native mouse chromosome 10 to evaluate the stability in Tc mice. The new MAC vector was transmitted through germline and stably maintained in the mouse tissues without any apparent abnormalities. Through this study, the potential of additional mouse centromere was demonstrated for Tc mouse production, and new MAC is expected to be used for various applications.