Severe Fanconi Anemia phenotypes in Fancd2 depletion mice.
Biochem Biophys Res Commun
; 514(3): 713-719, 2019 06 30.
Article
em En
| MEDLINE
| ID: mdl-31078270
ABSTRACT
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.
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Texto completo:
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteína do Grupo de Complementação D2 da Anemia de Fanconi
/
Anemia de Fanconi
Limite:
Animals
Idioma:
En
Revista:
Biochem Biophys Res Commun
Ano de publicação:
2019
Tipo de documento:
Article