Oscp1-KO Mouse

Oscp1, also known as NOR1 (Oxidored-nitro domain-containing protein 1), is a gene with multiple functions. It acts as a tumor suppressor, inhibiting cancer cell growth by disturbing tumor cell energy metabolism, promoting apoptosis in oxidative stress and hypoxia by inhibiting stress-induced autophagy, and suppressing epithelial-mesenchymal transition, invasion and metastasis via the FOXA1/HDAC2-slug regulatory network [1]. It also facilitates the transport of various organic solutes into cells [2,3]. In addition, Oscp1 may play roles in development, as its Drosophila ortholog dOSCP1 is involved in eye development, regulating apoptosis, proliferation, differentiation, and ROS generation [4].

In Drosophila, knockdown of dOSCP1 in eye imaginal discs led to a rough-eye phenotype due to caspase-dependent apoptosis, compensatory cell proliferation, ROS generation, and defects in cone and pigment cell differentiation [4]. Overexpression of dOSCP1 in eye imaginal discs also induced a rough-eye phenotype, along with endoplasmic reticulum stress in salivary gland cells [5]. In mice, the mouse ortholog of Oscp1 is expressed in spermatogenic cells in the testis, and in the brain where it is mainly located in the cytosol of neurons and its expression is developmentally regulated [2,6].

In summary, Oscp1 is a multifunctional gene involved in tumor suppression, solute transport, and development. Studies in Drosophila and mouse models have revealed its role in processes like cancer-related phenotypes, eye development, spermatogenesis, and neuronal function, providing insights into its potential significance in human malignancies and normal biological processes.

References:

1. Yi, Mei, Yang, Jianbo, Li, Wenjuan, Li, Guiyuan, Xiang, Bo. 2017. The NOR1/OSCP1 proteins in cancer: from epigenetic silencing to functional characterization of a novel tumor suppressor. In Journal of Cancer, 8, 626-635. doi:10.7150/jca.17579. https://pubmed.ncbi.nlm.nih.gov/28367242/

2. Hiratsuka, Kazuyuki, Yin, Shan-Ai, Ohtomo, Takayuki, Kurosawa, Tohru, Yamada, Junji. . Intratesticular localization of the organic solute carrier protein, OSCP1, in spermatogenic cells in mice. In Molecular reproduction and development, 75, 1495-504. doi:10.1002/mrd.20893. https://pubmed.ncbi.nlm.nih.gov/18324622/

3. Huu, Nguyen Tho, Yoshida, Hideki, Umegawachi, Takanari, Miyata, Seiji, Yamaguchi, Masamitsu. 2014. Structural characterization and subcellular localization of Drosophila organic solute carrier partner 1. In BMC biochemistry, 15, 11. doi:10.1186/1471-2091-15-11. https://pubmed.ncbi.nlm.nih.gov/24939707/

4. Huu, Nguyen Tho, Yoshida, Hideki, Yamaguchi, Masamitsu. 2015. Tumor suppressor gene OSCP1/NOR1 regulates apoptosis, proliferation, differentiation, and ROS generation during eye development of Drosophila melanogaster. In The FEBS journal, 282, 4727-46. doi:10.1111/febs.13528. https://pubmed.ncbi.nlm.nih.gov/26411401/

5. Huu, Nguyen Tho, Yoshida, Hideki, Yamaguchi, Masamitsu. 2015. Overexpression of tumor suppressor protein OSCP1/NOR1 induces ER stress and apoptosis during development of Drosophila melanogaster. In American journal of cancer research, 5, 1718-29. doi:. https://pubmed.ncbi.nlm.nih.gov/26175940/

6. Hiratsuka, Kazuyuki, Momose, Atsushi, Takagi, Norio, Kurosawa, Tohru, Yamada, Junji. 2011. Neuronal expression, cytosolic localization, and developmental regulation of the organic solute carrier partner 1 in the mouse brain. In Histochemistry and cell biology, 135, 229-38. doi:10.1007/s00418-011-0790-6. https://pubmed.ncbi.nlm.nih.gov/21331566/