Alternative titles; symbols
HGNC Approved Gene Symbol: CD33
Cytogenetic location: 19q13.41 Genomic coordinates (GRCh38): 19:51,211,076-51,240,016 (from NCBI)
The CD33 antigen, which can be recognized by the monoclonal antibodies My9, L1B2, and L4F3, is expressed exclusively by myeloid cells. Monoclonal antibodies of the CD33 cluster group recognize a 67-kD protein, designated p67 (summary by Peiper et al., 1987). Peiper et al. (1987) cloned the gene encoding p67.
By Southern blot analysis of DNA from human-hamster hybrid cells, Peiper et al. (1987) assigned the CD33 gene to chromosome 19. Peiper et al. (1988) sublocalized the CD33 gene to 19q13.3 by in situ hybridization. Adriaansen et al. (1990) confirmed the assignment of CD33 to chromosome 19 by a study of human-mouse hybrids constructed by fusion of human acute undifferentiated leukemia cells with mouse thymoma cells. By fluorescence in situ hybridization, Trask et al. (1993) mapped CD33 to 19q13.3-q13.4.
Naj et al. (2011) identified a single-nucleotide polymorphism upstream of the CD33 gene, rs3865444, as a risk allele for Alzheimer disease (see 104300) (metaanalysis p = 1.6 x 10(-9)).
Bradshaw et al. (2013) found that the risk allele, C, of rs3865444 was associated with greater cell surface expression of CD33 in the monocytes of young and older individuals (t(50) = 10.06, joint p = 1.3 x 10(-13)). It was also associated with diminished internalization of amyloid-beta-42 (APP; 104760) peptide, accumulation of neuritic amyloid pathology and fibrillar amyloid on in vivo imaging, and increased numbers of activated human microglia.
Mouse Model
Brinkman-Van der Linden et al. (2003) found that mouse Cd33 is expressed on myeloid precursors in the bone marrow, albeit mostly in the more mature stages of the granulocytic lineage. Moreover, unlike human CD33, mouse Cd33 in peripheral blood is primarily expressed on granulocytes. Unlike human CD33, mouse Cd33 did not bind to alpha-2-3- or alpha-2-6-linked sialic acids on lactosamine units. Instead, it showed distinctive sialic acid-dependent binding only to the short O-linked glycans of certain mucins. Mice deficient in Cd33 were viable and fertile in a controlled-access specific pathogen-free vivarium, showed no major morphologic or histologic abnormalities, had no changes in bone marrow or peripheral leukocyte subpopulations, and had very minor differences in biochemical and erythrocyte parameters. Cellular responses to intraperitoneally injected proinflammatory stimulants, as well as subsequent interleukin-6 (147620) secretion, were also apparently unaffected. Brinkman-Van der Linden et al. (2003) concluded that their results showed substantial species differences in CD33 expression patterns and ligand recognition and suggested functional redundancy between mouse Cd33 and the other CD33-related SIGLEC (see 600751) proteins expressed on cells of the myeloid lineage.
Adriaansen, H. J., Geurts Van Kessel, A. H. M., Wijdenes-De Bresser, J. H. F. M., Van Drunen-Schoenmaker, E., Van Dongen, J. J. M. Expression of the myeloid differentiation antigen CD33 depends on the presence of human chromosome 19 in human-mouse hybrids. Ann. Hum. Genet. 54: 115-119, 1990. [PubMed: 1696442] [Full Text: https://doi.org/10.1111/j.1469-1809.1990.tb00367.x]
Bradshaw, E. M., Chibnik, L. B., Keenan, B. T., Ottoboni, L., Raj, T., Tang, A., Rosenkrantz, L. L., Imboywa, S., Lee, M., Von Korff, A., The Alzheimer's Disease Neuroimaging Initiative, Morris, M. C., Evans, D. A., Johnson, K., Sperling, R. A., Schneider, J. A., Bennett, D. A., De Jager, P. L. CD33 Alzheimer's disease locus: altered monocyte function and amyloid biology. Nature Neurosci. 16: 848-850, 2013. [PubMed: 23708142] [Full Text: https://doi.org/10.1038/nn.3435]
Brinkman-Van der Linden, E. C. M., Angata, T., Reynolds, S. A., Powell, L. D., Hedrick, S. M., Varki, A. CD33/Siglec-3 binding specificity, expression pattern, and consequences of gene deletion in mice. Molec. Cell. Biol. 23: 4199-4206, 2003. [PubMed: 12773563] [Full Text: https://doi.org/10.1128/MCB.23.12.4199-4206.2003]
Naj, A. C., Jun, G., Beecham, G. W., Wang, L.-S., Vardarajan, B. N., Buros, J., Gallins, P. J., Buxbaum, J. D., Jarvik, G. P., Crane, P. K., Larson, E. B., Bird, T. D., and 143 others. Common variants at MS4A4/MS4A6E, CD2AP, CD33 and EPHA1 are associated with late-onset Alzheimer's disease. Nature Genet. 43: 436-441, 2011. [PubMed: 21460841] [Full Text: https://doi.org/10.1038/ng.801]
Peiper, S. C., Ashmun, R. A., Look, A. T. Molecular cloning, expression, and chromosomal localization of a human gene encoding the CD33 myeloid differentiation antigen. Blood 72: 314-321, 1988. [PubMed: 3390608]
Peiper, S. C., Lemons, R. S., Ashmun, R. A., Look, A. T. DNA-mediated transfer of the gene encoding p67 (CD33), a myeloid differentiation antigen recognized by the My9, L1B2, and L4F3 monoclonal antibodies.In: McMichael, A. J. : Leucocyte Typing III. Oxford: Oxford Univ. Press (pub.) 1987. Pp. 622-625.
Trask, B., Fertitta, A., Christensen, M., Youngblom, J., Bergmann, A., Copeland, A., de Jong, P., Mohrenweiser, H., Olsen, A., Carrano, A., Tynan, K. Fluorescence in situ hybridization mapping of human chromosome 19: cytogenetic band location of 540 cosmids and 70 genes or DNA markers. Genomics 15: 133-145, 1993. [PubMed: 8432525] [Full Text: https://doi.org/10.1006/geno.1993.1021]