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Role of ornithine decarboxylase antizyme inhibitor in vivo |
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| Authors: | Hua Tang Kimi Ariki Makiko Ohkido Yasuko Murakami Senya Matsufuji Zhenghua Li Ken-ichi Yamamura |
| Affiliation: | Key Laboratory of Molecular Infectious Diseases, Ministry of Education, Chongqing Medical University, Chongqing 400016, China; Department of Developmental Genetics, Institute of Molecular Embryology and Genetics, Kumamoto University, Kumamoto 860-0811, Japan; Department of Molecular Biology, The Jikei University School of Medicine, Minato-ku, Tokyo 105-8461, Japan; Faculty of Pharmacy, Research Institute of Pharmaceutical Sciences, Musashino University, Tokyo 202-8585, Japan |
| Abstract: | Ornithine decarboxylase (ODC) antizyme inhibitor (AZI) has been shown to regulate ODC activity in cell cultures. However, its biological functions in an organism remain unknown. An embryonic stem (ES) cell clone was established, in which the Azin1 gene was disrupted by the gene trap technique. To identify the function of Azin1 gene in vivo , a mutant mouse line was generated using these trapped ES cells. Homozygous mutant mice died at P0 with abnormal liver morphology. Further analysis indicated that the deletion of Azin1 in homozygous mice resulted in the degradation of ODC, and reduced the biosynthesis of putrescine and spermidine. Our results thus show that AZI plays an important role in regulating the levels of ODC, putrescine and spermidine in mice, and is essential for the survival of mice. |
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