Premature ovarian failure (POF) in women is characterized as menopause commencing before age 35. Although some cases of POF appear to be inherited, no experimental animal models of familial POF are available. Pellas et al. (1991) identified a mouse mutation that results in infertility due to a lack of primordial germ cells arising in early embryonic development. Duncan et al. (1993) observed that shortly after puberty, females homozygous for this mutation entered reproductive senescence as defined by high levels of circulating gonadotropins, inability to respond either hormonally or functionally to superovulation, and a disrupted estrous cycle. Also, the ovaries completely lacked developing follicles and the endometrium was inactive. However, these mice had undergone complete sexual development as determined by age of vaginal opening, mammary gland histology, and sexual behavior. Thus, these animals closely mimic familial premature ovarian failure and may be useful models for study of the pathogenesis and treatment of this condition.
NCBI Summary:
This gene encodes the complementation group L subunit of the multimeric Fanconi anemia (FA) nuclear complex composed of proteins encoded by over ten Fanconi anemia complementation (FANC) group genes. The FA complex is necessary for protection against DNA damage. This gene product, an E3 ubiquitin ligase, catalyzes and is required for the monoubiquitination of the protein encoded by the Fanconi anemia, complementation group D2 gene, a critical step in the FA pathway (PMID: 12973351, 21229326). In mouse, mutations of this E3 ubiquitin ligase gene can lead to infertility in adult males and females, and a deletion of this gene can cause embryonic lethality in some genetic backgrounds. A pseudogene of this gene has been identified on chromosome 1. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2013]
General function
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Cellular localization
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Ovarian function
Germ cell development, Germ cell migration
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Expression regulated by
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Ovarian localization
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Follicle stages
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Phenotypes
Mutations
1 mutations
Species: mouse
Mutation name: PCD
type: naturally occurring fertility: subfertile Comment:Pellas et al. (1993) isolated an insertional transgenic mouse mutant that results in abnormal germ-cell development.This recessive mutation manifests as infertility in both males and females and is specific for the reproductive organs, since all other tissues examined were histologically normal. A developmental analysis of the gonadal tissues demonstrated that germ cells were specifically depleted as early as day 11.5 of embryonic
development, while the various somatic cells were
apparently unaffected. Therefore, the mutated locus must play a critical role in the migration/proliferation of primordial germ cells to the genital ridges of developing embryos. In addition, females
homozygous for the mutation could potentially be a
valuable animal model of a human syndrome, premature ovarian failure.This mutation has been named germ-cell deficient, gcd. Female mice homozygous for the germ cell-deficient (gcd) mutation enter reproductive senescence prematurely due to a dearth of germ cells arising in embryonic development. Duncan et al. (1993) showed that the ovaries of young gcd/gcd animals are atrophic, composed of little more than stromal cells in a connective tissue matrix. By one year of age, 56 per cent of homozygotes have developed tubulostromal adenoma of the ovary while 100 percent wild-type and heterozygous littermates are phenotypically normal.