Mice with a targeted disruption of the Fanconi anemia homolog Fanca.
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.
Department of Clinical Genetics and Human Genetics, Free University Medical Center, Van der Boechorststraat 7, 1081 BT Amsterdam, The Netherlands.
N C
NC
Cheng
H J
HJ
van de Vrugt
M A
MA
van der Valk
A B
AB
Oostra
P
P
Krimpenfort
Y
Y
de Vries
H
H
Joenje
A
A
Berns
F
F
Arwert
D000818:Animals; D004268:DNA-Binding Proteins; D005199:Fanconi Anemia; D052217:Fanconi Anemia Complementation Group A Protein; D005260:Female; D018390:Gene Targeting; D006405:Hematology; D006801:Humans; D007247:Infertility, Female; D007248:Infertility, Male; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D010053:Ovary / Q000002:abnormalities / Q000473:pathology; D010641:Phenotype; D011506:Proteins / Q000235:genetics / Q000502:physiology*; D013737:Testis / Q000002:abnormalities / Q000473:pathology
D004268:DNA-Binding Proteins; C498471:FANCA protein, human; C120277:Fanca protein, mouse; D052217:Fanconi Anemia Complementation Group A Protein; D011506:Proteins