Inactivation of Fac in mice produces inducible chromosomal instability and reduced fertility reminiscent of Fanconi anaemia
| Autor: | Lili Liu, Dean H. Percy, Alexandra L. Joyner, Hagop Youssoufian, Jay Cross, Melvin H. Freedman, Ming Chen, Manuel Buchwald, John E. Dick, Darrell J. Tomkins, Olga I. Gan, Tim Groves, Wojtek Auerbach, Anna Auerbach, Colin McKerlie, Madeleine Carreau, Cynthia J. Guidos |
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| Rok vydání: | 1996 |
| Předmět: |
Male
Fanconi anemia complementation group C Genetic Vectors Diepoxybutane Genes Recessive Biology Mice chemistry.chemical_compound Fanconi anemia Chromosome instability Testis Genetics medicine Animals Cloning Molecular Allele Homozygote Ovary Bone marrow failure medicine.disease Molecular biology FANCB Complementation Fanconi Anemia chemistry Infertility Gene Targeting Mutation Immunology Female |
| Zdroj: | Nature Genetics. 12:448-451 |
| ISSN: | 1546-1718 1061-4036 |
| DOI: | 10.1038/ng0496-448 |
| Popis: | Fanconi anaemia (FA) is an autosomal recessive disease characterized by bone marrow failure, variable congenital malformations and predisposition to malignancies1,2. Cells derived from FA patients show elevated levels of chromosomal breakage and an increased sensitivity to bifunctional alkylating agents such as mitomycin C (MMC) and diepoxybutane (DEB)3,4. Five complementation groups have been identified by somatic cell methods5,6, and we have cloned the gene defective in group C (FAC)7. To understand the in vivo role of this gene, we have disrupted murine Fac and generated mice homozygous for the targeted allele. The −/− mice did not exhibit developmental abnormalities nor haematologic defects up to 9 months of age. However, their spleen cells had dramatically increased numbers of chromosomal aberrations in response to MMC and DEB. Homozygous male and female mice also had compromised gametogenesis, leading to markedly impaired fertility, a characteristic of FA patients2. Thus, inactivation of Fac replicates some of the features of the human disease. |
| Databáze: | OpenAIRE |
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