Disease relevance of Fancd2

• Heterozygosity for p53 (Trp53+/-) accelerates epithelial tumor formation in fanconi anemia complementation group D2 (Fancd2) knockout mice [1].

High impact information on Fancd2

• However, Fancd2 mutant mice also displayed phenotypes not observed in other mice with disruptions of proximal FA genes [2].
• Therefore, Trp53 is required for the S phase checkpoint activation observed in Fancd2 mutant cells [1].
• In addition, it was found that Fancd2(-/-) mouse embryonic fibroblasts but not Fancd2(-/-)/Trp53(-/-) mouse embryonic fibroblasts arrest following DNA damage [1].
• To further investigate the role of the FA pathway in tumor prevention, Fancd2 mutant mice were crossed to mice with a null mutation in the tumor suppressor gene, Trp53 [1].
• Homozygous germ line mutation in exon 27 of murine Brca2 disrupts the Fancd2-Brca2 pathway in the homologous recombination-mediated DNA interstrand cross-links' repair but does not affect meiosis [3].

Biological context of Fancd2

• We show that the targeted deletion of Fanca exons 37-39 generates a null for Fanca in mice and abolishes ubiquitination of Fancd2, the downstream effector of the FA complex [4].
• These data demonstrate not only that expression of this FAD gene causes neuronal apoptosis, but that F11/EcR/V642I cells, the first neuronal cells with inducible FAD gene expression, provide a useful model system in investigating AD disorders [5].

Anatomical context of Fancd2

• Quantitative electron microscopic immunocytochemistry revealed that by 6 months, the proportion of postsynaptic spines with drebrin A within somatosensory cortex layer I was smaller for the FAD model mice, when compared to the corresponding region of WT mice (P < 0.0005) [6].

Other interactions of Fancd2

• Immunoprecipitation experiments showed that Fancd2 did not coprecipitate with the mutated Brca2 [3].

References