Mice with a targeted disruption of the Fanconi anemia homolog Fanca

• Published in: Human molecular genetics Vol. 9; no. 12; pp. 1805 - 1811
• Main Authors: NGAN CHING CHENG, VAN DE VRUGT, H. J, VAN DER VALK, M. A, OOSTRA, A. B, KRIMPENFORT, P, DE VRIES, Y, JOENJE, H, BERNS, A, ARWERT, F
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 22.07.2000; Oxford Publishing Limited (England)
• Subjects: Anemias. Hemoglobinopathies; Animals; Biological and medical sciences; Diseases of red blood cells; DNA-Binding Proteins; Fanca gene; Fanconi Anemia; Fanconi Anemia Complementation Group A Protein; Female; Gene Targeting; Hematologic and hematopoietic diseases; Hematology; Humans; Infertility, Female; Infertility, Male; Male; Medical sciences; Mice; Mice, Knockout; mitomycin C; Ovary - abnormalities; Ovary - pathology; Phenotype; Proteins - genetics; Proteins - physiology; Testis - abnormalities; Testis - pathology; Chromosomal aberration; Genetic mapping; Chromosome fragility; Fanconi anemia; Targeting; Stem cell; Rodentia; Homology; Hemopathy; Genetic disease; Vertebrata; Mammalia; Gene; Mouse; Fertility; Mutation; Vector
• ISSN: 0964-6906; 1460-2083; 1460-2083
• DOI: 10.1093/hmg/9.12.1805

Fanconi anemia (FA) is a hereditary chromosomal instability syndrome with cancer predisposition. Bone marrow failure resulting in pancytopenia is the main cause of death of FA patients. Diagnosis of FA is based on their cellular hypersensitivity to DNA crosslinking agents and chromosome breakages. Somatic complementation experiments suggest the involvement of at least eight genes in FA. The gene for complementation group A (FANCA) is defective in the majority of FA patients. We show here that mice deficient of FANCA: are viable and have no detectable developmental abnormalities. The hematological parameters showed a slightly decreased platelet count and a slightly increased erythrocyte mean cell volume in mice at young age, but this did not progress to anemia. Consistent with the clinical phenotype of FA patients, both male and female mice showed hypogonadism and impaired fertility. Furthermore, embryonic fibroblasts of the knock-out mice exhibited spontaneous chromosomal instability and were hyper-responsive to the clastogenic effect of the crosslinker mitomycin C.