Fam210b-KO Mouse

Fam210b, encoding a mitochondrial inner membrane protein, is involved in multiple biological processes. It has been linked to mitochondrial metabolism, iron homeostasis, and erythropoiesis. In erythroid cells, it is a target of GATA-1 and erythropoietin, and is associated with pathways regulating heme synthesis and mitochondrial energy metabolism [2,5,7]. Genetic models, such as knockout mice, are valuable for studying its functions.

In adult mice, Fam210b-/-mice are viable, with no erythropoietic defects in the bone marrow, although there are some modest phenotypes like increased lymphocytes in females and body weight in males. This suggests that while Fam210b may be important for erythroid differentiation and heme synthesis under standard cell culture conditions, it may play a more crucial role in cellular iron homeostasis during iron-deficient conditions [1]. In contrast, in human induced pluripotent stem-derived erythroid progenitor cells, depletion of Fam210B led to more pronounced erythroid differentiation, along with changes in mitochondrial energy metabolism [2]. Also, Fam210b knockout in mice led to abnormal erythrocyte differentiation in the spleen, with an increased number of CD71+ erythroid cells and elevated ROS levels, and approximately 15.68% of these mice spontaneously developed lupus-like autoimmunity [3]. A Mendelian randomization study indicated that genetically reduced expression of FAM210B was associated with an increased risk of drug-induced lupus [4]. In hepatocellular carcinoma, depletion of FAM210B increased cell growth, migration, and invasion, while overexpression suppressed tumor growth in a xenograft model, and it was involved in MAPK and p-AKT signaling pathways [6].

In summary, Fam210b plays important roles in erythropoiesis, mitochondrial metabolism, and iron homeostasis. Its knockout mouse models have revealed associations with diseases such as systemic lupus erythematosus and drug-induced lupus, as well as its role in tumor growth in hepatocellular carcinoma. These findings enhance our understanding of the biological functions of Fam210b and its implications in disease mechanisms.

References:

1. Perfetto, Mark, Rondelli, Catherine M, Gillis, Samantha, Stratman, Amber N, Yien, Yvette Y. 2023. FAM210B is dispensable for erythroid differentiation in adult mice. In bioRxiv : the preprint server for biology, , . doi:10.1101/2023.09.26.559581. https://pubmed.ncbi.nlm.nih.gov/37823037/

2. Suzuki, Chie, Fujiwara, Tohru, Shima, Hiroki, Igarashi, Kazuhiko, Harigae, Hideo. 2022. Elucidation of the Role of FAM210B in Mitochondrial Metabolism and Erythropoiesis. In Molecular and cellular biology, 42, e0014322. doi:10.1128/mcb.00143-22. https://pubmed.ncbi.nlm.nih.gov/36374104/

3. Xu, Yaqi, Gao, Ran, Zhang, Min, Su, Wenting, Wang, Renxi. 2024. Deletion of the Mitochondrial Membrane Protein Fam210b Is Associated with the Development of Systemic Lupus Erythematosus. In International journal of molecular sciences, 25, . doi:10.3390/ijms25137253. https://pubmed.ncbi.nlm.nih.gov/39000360/

4. Xu, Yaqi, Gao, Ran, Zhang, Min, Su, Wenting, Wang, Renxi. 2024. Mendelian randomization study on causal association of FAM210B with drug-induced lupus. In Clinical rheumatology, 43, 1513-1520. doi:10.1007/s10067-024-06903-w. https://pubmed.ncbi.nlm.nih.gov/38436771/

5. Yien, Yvette Y, Shi, Jiahai, Chen, Caiyong, Lodish, Harvey F, Paw, Barry H. 2018. FAM210B is an erythropoietin target and regulates erythroid heme synthesis by controlling mitochondrial iron import and ferrochelatase activity. In The Journal of biological chemistry, 293, 19797-19811. doi:10.1074/jbc.RA118.002742. https://pubmed.ncbi.nlm.nih.gov/30366982/

6. Zhou, Yuanqin, Pan, Xianzhu, Liu, Yakun, Kan, Chen, Zheng, Hong. 2023. Loss of the Novel Mitochondrial Membrane Protein FAM210B Is Associated with Hepatocellular Carcinoma. In Biomedicines, 11, . doi:10.3390/biomedicines11041232. https://pubmed.ncbi.nlm.nih.gov/37189851/

7. Fujiwara, Tohru. . [Mitochondrial metabolism and erythroid differentiation]. In [Rinsho ketsueki] The Japanese journal of clinical hematology, 65, 183-187. doi:10.11406/rinketsu.65.183. https://pubmed.ncbi.nlm.nih.gov/38569864/