Zebrafish Model Of Fanconi Anemia

Regarding Fanconi anemia (FA), researchers have recently turned to zebrafish to help them unravel conserved signaling pathways (Liu et al., 2003). Although FA is a relatively rare genetic disease, the genes involved in FA function as part of a large network of DNA damage response/repair, and the phenotypic features of FA consist of a combination of developmental and somatic abnormalities, including alterations reminiscent of premature aging (Giannelli, 1986; Tischkowitz and Hodgson, 2003; Willingale-Theune et al., 1989). Liu and colleagues have recapitulated some of the clinical manifestations of human FA by knocking down the zebrafish FANC-D2 gene, thereby providing a new model for probing the underlying causes of these phenotypes (Liu et al., 2003). They have identified the zebrafish homolog of human FANCD2, which encodes a nuclear effecter protein that is monoubiquitinated in response to DNA damage, targeting it to nuclear foci where it preserves chromosomal integrity. Fancd2-knockdown zebrafish embryos developed defects similar to those found in children with FA, including shortened body length, microcephaly, and microophthalmia, which are due to extensive cellular apoptosis. Intriguingly, developmental defects and increased apoptosis in Fancd2-knockdown zebrafish are corrected by injection of human Fancd2 or zebrafish bcl-2 mRNA, or by knockdown of p53, indicating that in the absence of Fancd2, developing tissues spontaneously undergo p53-dependent apoptosis. Thus, Fancd2 is essential during embryogenesis to prevent inappropriate apoptosis in neural cells and other tissues undergoing high levels of proliferative expansion, implicating this mechanism in the congenital abnormalities observed in human infants with FA.

Although characterizations of premature senescence phenotypes in the zebrafish FA model are still needed, taking into account molecular interaction and signaling crosstalk between Fancd2 and ATM (Taniguchi et al.,

2002), FA and A-T will be one of the most prominent genetic diseases for the zebrafish models of human ''premature aging syndromes.''

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Blood Pressure Health

Your heart pumps blood throughout your body using a network of tubing called arteries and capillaries which return the blood back to your heart via your veins. Blood pressure is the force of the blood pushing against the walls of your arteries as your heart beats.Learn more...

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