Alternative titles; symbols
HGNC Approved Gene Symbol: SPON2
Cytogenetic location: 4p16.3 Genomic coordinates (GRCh38): 4:1,166,932-1,208,844 (from NCBI)
Using a differential display technique, Manda et al. (1999) isolated 2 novel cDNAs, SPON2 and C20ORF1 (605917), which they designated differentially expressed in cancerous and noncancerous lung cells-1 (DIL1) and -2 (DIL2), respectively. The full-length SPON2 cDNA encodes a 331-amino acid protein with a domain organization similar to those of zebrafish mindin-1/mindin-2 and F-spondin (SPON1; 604989): a hydrophobic signal sequence in the N terminus, an FS1 domain, an FS2 domain, and a thrombospondin type I repeat. RT-PCR analysis detected no expression of SPON2 in lung carcinoma cells. Northern blot analysis detected expression of a 1.9-kb SPON2 transcript in various tissues, including adult and fetal lung.
He et al. (2004) cloned mouse Spon2, which they termed mindin. The mouse mindin protein, which is 85% identical to the human protein, is a conserved member of a family of secreted extracellular matrix proteins. RNA blot analysis detected expression in a variety of tissues, with abundant expression in lung and lymphoid tissues. Immunoblot blot analysis showed expression of a 42-kD protein under reducing conditions and expression of dimers and oligomers in a concentration-dependent manner under nonreducing conditions.
He et al. (2004) determined that the mouse Spon2 gene contains 6 exons spanning 5 kb.
The International Radiation Hybrid Mapping Consortium mapped the SPON2 gene to chromosome 4p16.3 (WI-22263).
By targeted replacement of part of exon 1 and all of exons 2 and 3 of the Spon2 gene, He et al. (2004) generated Spon2-deficient mice. These mice had a normal appearance and life span under pathogen-free conditions. Spon2-deficient mice were resistant to lipopolysaccharide (LPS)-induced shock, and their macrophages only produced slightly elevated inflammatory cytokines. Addition of Spon2 to Spon2-deficient, but not Tlr4 (603030)-deficient, macrophages restored their ability to produce inflammatory cytokines in response to LPS. Stimuli from most gram-positive and gram-negative bacteria and yeast also failed to induce cytokine responses from Spon2-deficient macrophages and mast cells. Spon2-deficient mice showed variable clearance of pathogens when inoculated by the pulmonary and intraperitoneal routes. Fluorescence microscopy demonstrated Spon2-dependent bacterial agglutination in the presence of calcium due to a specific interaction with the carbohydrate moiety of LPS and lipoteichoic acid. Phagocytosis experiments indicated that Spon2 acts as an opsonin and pattern-recognition molecule for a range of pathogens. He et al. (2004) proposed that Spon2 recognition of carbohydrate structures is essential for the activation of macrophages by pathogen-associated molecular patterns (PAMPs).
He, Y.-W., Li, H., Zhang, J., Hsu, C.-L., Lin, E., Zhang, N., Guo, J., Forbush, K. A., Bevan, M. J. The extracellular matrix protein mindin is a pattern-recognition molecule for microbial pathogens. Nature Immun. 5: 88-97, 2004. [PubMed: 14691481] [Full Text: https://doi.org/10.1038/ni1021]
Manda, R., Kohno, T., Matsuno, Y., Takenoshita, S., Kuwano, H., Yokota, J. Identification of genes (SPON2 and C20orf2) differentially expressed between cancerous and noncancerous lung cells by mRNA differential display. Genomics 61: 5-14, 1999. [PubMed: 10512675] [Full Text: https://doi.org/10.1006/geno.1999.5939]