CUZD1, the CUB and zona pellucida-like domains-containing protein 1, is expressed in mammary ductal and alveolar epithelium. It is a critical mediator of the JAK/STAT5 signaling pathway, regulating the expression of EGF family growth factors during mammary gland development in pregnancy and lactation [2]. CUZD1 is also of interest in the context of diseases. It is a target of pancreatic autoantibodies in inflammatory bowel diseases, especially Crohn's disease, and is associated with certain clinical phenotypes like ileocolonic and perianal disease [1,3,4,5]. Moreover, it has potential as a biomarker in cancer, with mRNA overexpression in ovarian cancer and elevated serum levels in ovarian and pancreatic cancer patients [1].

In Cuzd1 -null mice, there is a significant impairment in mammary ductal branching and alveolar development during pregnancy, leading to lactation defects. Gene expression profiling shows that CUZD1 regulates the expression of epiregulin, neuregulin-1, and epigen in the mammary epithelium. Proteomic studies reveal its interaction with a complex containing JAK1/JAK2 and STAT5, and its absence abolishes STAT5 phosphorylation during alveologenesis. Conversely, elevated Cuzd1 expression stimulates prolactin-induced phosphorylation and nuclear translocation of STAT5 [2].

In conclusion, CUZD1 plays a crucial role in mammary gland development through its involvement in the JAK/STAT5 signaling pathway. Its association with inflammatory bowel diseases and potential as a cancer biomarker make it an important gene for study. The Cuzd1 -null mouse model has been instrumental in revealing its role in mammary gland development, providing insights into both normal physiological processes and potential disease mechanisms related to this gene [2].

References:

1. Liaskos, Christos, Rigopoulou, Eirini I, Orfanidou, Timoklia, Bogdanos, Dimitrios P, Papandreou, Christos N. 2013. CUZD1 and anti-CUZD1 antibodies as markers of cancer and inflammatory bowel diseases. In Clinical & developmental immunology, 2013, 968041. doi:10.1155/2013/968041. https://pubmed.ncbi.nlm.nih.gov/23710207/

2. Mapes, Janelle, Li, Quanxi, Kannan, Athilakshmi, Bagchi, Indrani C, Bagchi, Milan K. 2017. CUZD1 is a critical mediator of the JAK/STAT5 signaling pathway that controls mammary gland development during pregnancy. In PLoS genetics, 13, e1006654. doi:10.1371/journal.pgen.1006654. https://pubmed.ncbi.nlm.nih.gov/28278176/

3. Michaels, Maike Anna, Jendrek, Sebastian Torben, Korf, Tobias, Fellerman, Klaus, Sina, Christian. . Pancreatic Autoantibodies Against CUZD1 and GP2 Are Associated with Distinct Clinical Phenotypes of Crohn's Disease. In Inflammatory bowel diseases, 21, 2864-72. doi:10.1097/MIB.0000000000000564. https://pubmed.ncbi.nlm.nih.gov/26273818/

4. Pavlidis, Polychronis, Komorowski, Lars, Teegen, Bianca, Forbes, Alastair, Bogdanos, Dimitrios P. . Diagnostic and clinical significance of Crohn's disease-specific pancreatic anti-GP2 and anti-CUZD1 antibodies. In Clinical chemistry and laboratory medicine, 54, 249-56. doi:10.1515/cclm-2015-0376. https://pubmed.ncbi.nlm.nih.gov/26351932/

5. Farkona, Sofia, Soosaipillai, Antoninus, Filippou, Panagiota, Diamandis, Eleftherios P, Blasutig, Ivan M. . Novel immunoassays for detection of CUZD1 autoantibodies in serum of patients with inflammatory bowel diseases. In Clinical chemistry and laboratory medicine, 55, 1574-1581. doi:10.1515/cclm-2016-1120. https://pubmed.ncbi.nlm.nih.gov/28343172/