Disease relevance of Fancl

• The germ cell-deficient (gcd) mouse mutation is a recessive, transgenic insertional mutation associated with the disruption of two Chr11 genes, Pog (proliferation of germ cells) and Vrk2 (vaccinia virus-related protein kinase 2) [1].
• Germ-cell deficient (gcd), an insertional mutation manifested as infertility in transgenic mice [2].
• Deletion of Pog is also accompanied by reduced embryonic body weight and, on some genetic backgrounds, embryonic lethality [3].
• Germ cell deficient (gcd) mouse as a model of premature ovarian failure [4].
• Because PHF9 is defective in a cell line derived from an individual with Fanconi anemia, we conclude that PHF9 (also called FANCL) represents a novel Fanconi anemia complementation group (FA-L) [5].

High impact information on Fancl

• This mutation has been named germ-cell deficient, gcd [2].
• Thus, in addition to being necessary for PGC proliferation, Pog may have a wider significance in early embryonic development [3].
• We report here that the mouse gcd (germ cell deficient) mutant phenotype, characterized by reduced numbers of PGCs and adult sterility, is due to reduced PGC proliferation rather than aberrant migration and is caused by the partial deletion of a single novel gene, Pog (proliferation of germ cells) [3].
• Mouse Ggn and Pog were both expressed in primary spermatocytes [6].
• Here we show that Pog is also involved in spermatogenesis in that meiosis is impaired in Pog-deficient mice [6].

Biological context of Fancl

• While GGN2, another protein from Ggn by alternative splicing did not interact with FANCL/POG since it lacked the domain mediating the interaction [7].
• We have recently shown that like gcd/gcd mice, targeted Pog-/- males and females show virtually no spermatogenesis or oogenesis at 4-6 wk of age [1].
• DAPI chromosomal banding in conjunction with double labeling with the alpha 1(I) collagen gene revealed that the gcd locus is situated on mouse Chromosome (Chr) 11A2-3 [8].
• To confirm the activity and specificity of the FANCL antibody, we constructed plasmid pCMV-HA/FANCL to transfect HEK 293T cells [9].
• Fanconi anemia complementation group L (FANCL) is a novel Fanconi anemia protein, which mono-ubiquitinates FANCD2 as a ubiquitin E3 ligase, and plays a crucial role in DNA damage repair and chromosome stability maintenance [9].

Anatomical context of Fancl

• The germ cell-deficient (gcd) mutation is a recessive transgenic insertional mutation leading to a deficiency of primordial germ cells (PGCs) [6].
• The ovaries of young gcd/gcd animals are atrophic, composed of little more than stromal cells in a connective tissue matrix [10].
• We found wide expression of FANCL in brain, muscle, heart, lung, liver, spleen, kidney, testis, ovary and uterus, indicating the functional importance of this novel protein [9].

Analytical, diagnostic and therapeutic context of Fancl

• Since the gcd mutation arose from the insertion of over 100 kb of foreign DNA into the chromosome during a transgenic mouse experiment, fluorescent in situ hybridization with the transgene as a probe was used to determine the chromosomal position of the gcd locus [8].
• The antibody was used in Western blotting to check the expression of FANCL protein in mouse tissues [9].
• Transiently expressed HA-FANCL fusion protein was analyzed by immunoblotting with both the FANCL antibody and HA monoclonal antibody [9].

References