期刊
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
卷 514, 期 3, 页码 713-719出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2019.04.201
关键词
Fanconi anemia; FANCD2; Mouse model; Crispr-Cas9
资金
- National Natural Science Foundation of China, China [3170080769]
- National Natural Science Foundation of Zhejiang Province, China [LY17H080009]
- Science and Technology Commission of Zhejiang Province, China [2017C37135, 2017F10007]
- Qianjiang Talent Fund, China [QJD1803033]
Fanconi anemia (FA) is a genetic disorder characterized by congenital malfunction, bone marrow failure and hypersensitivity to DNA damage. FANCD2 protein play the central role in FA pathway. To study the in vivo role of FANCD2, we generated and characterized a new Fancd2 knockout mouse strain with 7bp deletion in Fancd2 gene 5' terminus using Crispr-Cas9 in congenic C57BL/6J background. This Fancd2(-/-) mice displayed similar but overall more severe manifestation than the previous ES cell targeted Fancd2 model. These features include increased embryonic and postnatal lethality rate, higher incidence of microphthalmia, and more severe hypogonadism. The anemia we observed in this Fancd2(-/-) mice has not been described in other FA models. Further study indicated that the hematopoiesis deficiency was associated with increased apoptotic cell death, G2/M phase arrest and hypersensitivity to MMC and IR damage of Fancd2(-/-) bone marrow progenitor cells. Collectively, the resulting Fancd2(-/-) mice with higher resemblance of FA patient symptoms, will be useful in understand the parthenogenesis of pancytopenia and bone marrow failure in FA. (C) 2019 Elsevier Inc. All rights reserved.
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