Fem1a-KO Mouse

Fem1a, the human homologs of which are FEM1A, FEM1B, and FEM1C, is a gene with multiple functions. It is involved in the sex determination pathway in Caenorhabditis elegans and may have a related role in mammalian hedgehog signaling [2,3]. Fem1a proteins are substrate recognition subunits of CUL2-RING E3 ubiquitin ligase complexes, regulating the degradation of certain proteins like Stem-Loop Binding Protein (SLBP) [4].

In Rhabdomyosarcoma (RMS), Fem1a expression is downregulated in human RMS cell lines and in primary RMS from multiple mouse genetic models such as Ptch1+/-, p53-/-, p53+/-;Ptch1+/-, and HGF/SF-Ink4a/Arf-/- mice, suggesting its potential role in RMS pathogenesis [2]. In polycystic ovary syndrome (PCOS), certain FEM1A single nucleotide polymorphisms (SNPs) are associated with PCOS and related phenotypes. For example, SNPs rs8111933 and rs12460989 are associated with an increased likelihood of PCOS, while rs1044386 is associated with a reduced probability [1]. In Chinese Han patients, specific genotypes of FEM1A gene loci rs12460989 and rs8111933 are associated with PCOS and may be risk factors for hyperandrogenism and insulin resistance [5].

In conclusion, Fem1a plays important roles in processes related to muscle-associated diseases like RMS and in endocrine disorders such as PCOS. Mouse genetic models have been valuable in revealing its role in RMS, showing consistent downregulation in primary RMS. In PCOS, genetic studies on FEM1A have identified SNPs and genotypes associated with the disease, providing insights into its potential contribution to PCOS pathogenesis.

References:

1. Goodarzi, M O, Maher, J F, Cui, J, Taylor, K D, Azziz, R. 2008. FEM1A and FEM1B: novel candidate genes for polycystic ovary syndrome. In Human reproduction (Oxford, England), 23, 2842-9. doi:10.1093/humrep/den324. https://pubmed.ncbi.nlm.nih.gov/18757445/

2. Ventura-Holman, Tereza, Hahn, Heidi, Subauste, Jose S, Maher, Joseph F. 2005. The Fem1a gene is downregulated in Rhabdomyosarcoma. In Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine, 26, 294-9. doi:. https://pubmed.ncbi.nlm.nih.gov/16254458/

3. Krakow, D, Sebald, E, King, L M, Cohn, D H. . Identification of human FEM1A, the ortholog of a C. elegans sex-differentiation gene. In Gene, 279, 213-9. doi:. https://pubmed.ncbi.nlm.nih.gov/11733146/

4. Dankert, John F, Pagan, Julia K, Starostina, Natalia G, Kipreos, Edward T, Pagano, Michele. 2017. FEM1 proteins are ancient regulators of SLBP degradation. In Cell cycle (Georgetown, Tex.), 16, 556-564. doi:10.1080/15384101.2017.1284715. https://pubmed.ncbi.nlm.nih.gov/28118078/

5. Lin, Yuan, Sun, Yan. . [Polymorphisms of FEM1A gene in patients with polycystic ovary syndrome]. In Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical genetics, 29, 338-42. doi:10.3760/cma.j.issn.1003-9406.2012.03.020. https://pubmed.ncbi.nlm.nih.gov/22678803/