Cd320, also known as the transcobalamin receptor, is a type I transmembrane protein that plays a crucial role in the cellular uptake of vitamin B12 in peripheral tissues [2]. It is involved in the receptor-mediated endocytosis process of vitamin B12, which is essential for hematopoiesis and myelination [3]. The gene is associated with the vitamin B12-TCN2-CD320 signaling pathway, and its function is vital for maintaining normal physiological functions related to vitamin B12 metabolism [1]. Genetic models, such as the Cd320 knockout mouse, are valuable tools for studying its function.

In the Cd320-/-mouse, cobalamin deficiency occurs in the nervous system along with mild anemia [4]. Structural pathology in the spinal cord shows myelin loss in axonal tracts with inflammation, and the sciatic nerve indicates signs of demyelination and remyelination. Functionally, these mice have an increased latency to thermal nociception and a lower amplitude of compound action potential in the sciatic nerve, suggesting compromised function of myelinated axons and loss of peripheral sensation [4]. In cell culture studies, fibroblasts from CD320 p.E88del homozygotes, a variant in the Cd320 gene, exhibit reduced binding and uptake of cobalamin [5].

In conclusion, Cd320 is essential for vitamin B12 cellular uptake and metabolism. Studies using Cd320 knockout mouse models have revealed its significance in maintaining the structural and functional integrity of the nervous system. Understanding Cd320's function provides insights into the pathophysiology of vitamin B12-related neurological deficits and potentially other diseases associated with abnormal vitamin B12 metabolism [4,5].

References:

1. Jonnalagadda, Deepa, Kihara, Yasuyuki, Groves, Aran, Rivera, Richard, Chun, Jerold. 2023. FTY720 requires vitamin B12-TCN2-CD320 signaling in astrocytes to reduce disease in an animal model of multiple sclerosis. In Cell reports, 42, 113545. doi:10.1016/j.celrep.2023.113545. https://pubmed.ncbi.nlm.nih.gov/38064339/

2. Chen, Yue, Gu, Xiabing, Zhang, Yikai, Dong, Ningzheng, Wu, Qingyu. 2022. CD320 expression and apical membrane targeting in renal and intestinal epithelial cells. In International journal of biological macromolecules, 201, 85-92. doi:10.1016/j.ijbiomac.2021.12.158. https://pubmed.ncbi.nlm.nih.gov/34998874/

3. Pluvinage, John V, Ngo, Thomas, Fouassier, Camille, Pleasure, Samuel J, Wilson, Michael R. 2024. Transcobalamin receptor antibodies in autoimmune vitamin B12 central deficiency. In Science translational medicine, 16, eadl3758. doi:10.1126/scitranslmed.adl3758. https://pubmed.ncbi.nlm.nih.gov/38924428/

4. Arora, Kaveri, Sequeira, Jeffrey M, Alarcon, Juan M, Bottiglieri, Teodoro, Quadros, Edward V. 2018. Neuropathology of vitamin B12 deficiency in the Cd320-/- mouse. In FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 33, 2563-2573. doi:10.1096/fj.201800754RR. https://pubmed.ncbi.nlm.nih.gov/30303736/

5. Pangilinan, Faith, Watkins, David, Bernard, David, Kay, Denise M, Brody, Lawrence C. 2022. Probing the functional consequence and clinical relevance of CD320 p.E88del, a variant in the transcobalamin receptor gene. In American journal of medical genetics. Part A, 188, 1124-1141. doi:10.1002/ajmg.a.62627. https://pubmed.ncbi.nlm.nih.gov/35107211/