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Gene Review

C1qa  -  complement component 1, q subcomponent,...

Mus musculus

Synonyms: AI255395, C1q, Complement C1q subcomponent subunit A
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Disease relevance of C1qa


Psychiatry related information on C1qa


High impact information on C1qa

  • These findings are compatible with the hypothesis that C1q deficiency causes autoimmunity by impairment of the clearance of apoptotic cells [1].
  • The phenotype associated with C1q deficiency was modified by background genes [1].
  • Similarly, no IL-4 response or CD8(+) T-cell priming was seen in C1qa(-/-) mice [6].
  • However, mice deficient in C3, C1q, Bf/C2, combinations thereof or complement receptors were partially or fully protected against spongiform encephalopathy upon intraperitoneal exposure to limiting amounts of prions [7].
  • Thus, in the early stages of infection, C3 and perhaps C1q contribute to the localization of TSE infectivity in lymphoid tissue and may be therapeutic targets [8].

Chemical compound and disease context of C1qa


Biological context of C1qa

  • To assess the contribution of background genes in the expression of the autoimmune phenotype, the disrupted C1qa gene was backcrossed for seven generations onto C57BL/6 and MRL/Mp(+/+) strains [13].
  • Here, we studied the effect of BMT on autoimmunity in C1qa(-/-) mice [2].
  • Remarkably, this up-regulation did not occur in mice that lack an early factor of the complement cascade, C1q, a component which has been shown previously to facilitate early prion pathogenesis [14].
  • In this work we addressed the issue of whether genetic polymorphisms affecting C1q levels may predispose to SLE, using the (NZB x NZW)F(1) model [3].
  • Sequence analysis of the C1q gene in New Zealand Black (NZB), New Zealand White (NZW), and BALB/c mice showed no polymorphisms in exons and introns of three genes [3].

Anatomical context of C1qa

  • B cell tolerance was intact in C1qa-/- mice [15].
  • Following irradiation, young C1qa(-/-) or wild-type MRL/Mp mice received bone marrow cells (BMC) from strain-matched wild-type or C1qa(-/-) animals [2].
  • The frequency of anti-HEL-producing plasma cells and serum levels of anti-HEL immunoglobulin were comparably reduced in control and C1qa-/- double-transgenic mice compared to control Ig(HEL) and C1qa-/- Ig(HEL) mice [15].
  • C1q levels in sera and culture supernatants of LPS-stimulated peritoneal macrophages and C1q messages in spleen cells were all lower in disease-free young NZB and (NZB x NZW)F(1) mice than in age-matched non-autoimmune NZW and BALB/c mice [3].
  • GI/R significantly increased serum alanine aminotransferase, gastrointestinal barrier dysfunction, and neutrophil infiltration into the lung and gut in C1q KO and WT, but not C2/fB KO, mice [4].

Associations of C1qa with chemical compounds

  • IgG was detected in the glomeruli of diseased C1qa/H2-Bf/C2-/- kidneys [9].
  • These findings support the hypothesis that C1q may play a role in the clearance of apoptotic cells without the necessity for C3 activation and demonstrate that the activation of C3 is not essential for the development of GN in this spontaneous model of lupus-like disease [9].
  • Although most anti-CD20 antibodies activated complement in vitro, B cell depletion was completely effective in mice with genetic deficiencies in C3, C4, or C1q complement components [16].
  • We now report that the alpha2beta1 integrin is a novel receptor for multiple collectins and the C1q complement protein [17].
  • The multiple Fcs present in a single molecule apparently allow for more efficient interactions with the multiple C1q heads present in C1, the first component of the classical C cascade [18].

Physical interactions of C1qa

  • Under low ionic strength conditions, this mutant was found to be approximately 50 and 75% as active as wild-type IgG1 in the C1q binding and C4b deposition assays, respectively [19].
  • In this configuration, C1q bound avidly to PrP, with a K(D) of 5.4 nM (k(on) = 2.4 x 10(5) M(-1) s(-1); k(off) = 1.3 x 10(-3) s(-1)) [20].
  • gC1qBP is a 33 kDa glycoprotein that binds to the globular 'heads' of C1q [21].
  • In addition, we mutated the Glu 333, which resides in close proximity to the postulated C1q-binding site of mouse IgG2b, as well as Leu 235 in the lower hinge region [22].

Other interactions of C1qa

  • Lung injury in mice after GI/R is MBL and C1q independent, but C2 dependent, suggesting a potential role for ficolins in this model [4].
  • We used mice deficient in C1q, factor D, C3, and CD59, and compared them with strain-matched controls [23].
  • C4 binding studies, however, revealed that the observed difference in antibody and C1q binding has no influence on the complement resistance of SK-MEL-170 cells: significantly more C4b was bound to complement-resistant (1565 +/- 92 fg/cell) as compared to susceptible cells (715 +/- 31 fg/cell) [24].
  • Activation of human microglia by fibrillar prion protein-related peptides is enhanced by amyloid-associated factors SAP and C1q [25].
  • Characterisation of the rat and mouse homologues of gC1qBP, a 33 kDa glycoprotein that binds to the globular 'heads' of C1q [21].

Analytical, diagnostic and therapeutic context of C1qa


  1. Homozygous C1q deficiency causes glomerulonephritis associated with multiple apoptotic bodies. Botto, M., Dell'Agnola, C., Bygrave, A.E., Thompson, E.M., Cook, H.T., Petry, F., Loos, M., Pandolfi, P.P., Walport, M.J. Nat. Genet. (1998) [Pubmed]
  2. Restoration of C1q levels by bone marrow transplantation attenuates autoimmune disease associated with C1q deficiency in mice. Cortes-Hernandez, J., Fossati-Jimack, L., Petry, F., Loos, M., Izui, S., Walport, M.J., Cook, H.T., Botto, M. Eur. J. Immunol. (2004) [Pubmed]
  3. C1q regulatory region polymorphism down-regulating murine c1q protein levels with linkage to lupus nephritis. Miura-Shimura, Y., Nakamura, K., Ohtsuji, M., Tomita, H., Jiang, Y., Abe, M., Zhang, D., Hamano, Y., Tsuda, H., Hashimoto, H., Nishimura, H., Taki, S., Shirai, T., Hirose, S. J. Immunol. (2002) [Pubmed]
  4. Gastrointestinal ischemia-reperfusion injury is lectin complement pathway dependent without involving C1q. Hart, M.L., Ceonzo, K.A., Shaffer, L.A., Takahashi, K., Rother, R.P., Reenstra, W.R., Buras, J.A., Stahl, G.L. J. Immunol. (2005) [Pubmed]
  5. Absence of C1q leads to less neuropathology in transgenic mouse models of Alzheimer's disease. Fonseca, M.I., Zhou, J., Botto, M., Tenner, A.J. J. Neurosci. (2004) [Pubmed]
  6. Natural antibodies and complement are endogenous adjuvants for vaccine-induced CD8+ T-cell responses. Stäger, S., Alexander, J., Kirby, A.C., Botto, M., Rooijen, N.V., Smith, D.F., Brombacher, F., Kaye, P.M. Nat. Med. (2003) [Pubmed]
  7. Complement facilitates early prion pathogenesis. Klein, M.A., Kaeser, P.S., Schwarz, P., Weyd, H., Xenarios, I., Zinkernagel, R.M., Carroll, M.C., Verbeek, J.S., Botto, M., Walport, M.J., Molina, H., Kalinke, U., Acha-Orbea, H., Aguzzi, A. Nat. Med. (2001) [Pubmed]
  8. Temporary depletion of complement component C3 or genetic deficiency of C1q significantly delays onset of scrapie. Mabbott, N.A., Bruce, M.E., Botto, M., Walport, M.J., Pepys, M.B. Nat. Med. (2001) [Pubmed]
  9. Cutting edge: C1q protects against the development of glomerulonephritis independently of C3 activation. Mitchell, D.A., Taylor, P.R., Cook, H.T., Moss, J., Bygrave, A.E., Walport, M.J., Botto, M. J. Immunol. (1999) [Pubmed]
  10. Complement component C3 is not required for full expression of immune complex glomerulonephritis in MRL/lpr mice. Sekine, H., Reilly, C.M., Molano, I.D., Garnier, G., Circolo, A., Ruiz, P., Holers, V.M., Boackle, S.A., Gilkeson, G.S. J. Immunol. (2001) [Pubmed]
  11. Isolation and characterization of mouse C1q. McManus, L.M., Nakane, P.K. J. Immunol. Methods (1980) [Pubmed]
  12. Autoreactivity to mouse C1q in a murine model of SLE. Trinder, P.K., Maeurer, M.J., Schorlemmer, H.U., Loos, M. Rheumatol. Int. (1995) [Pubmed]
  13. C1q deficiency and autoimmunity: the effects of genetic background on disease expression. Mitchell, D.A., Pickering, M.C., Warren, J., Fossati-Jimack, L., Cortes-Hernandez, J., Cook, H.T., Botto, M., Walport, M.J. J. Immunol. (2002) [Pubmed]
  14. Immunologically induced, complement-dependent up-regulation of the prion protein in the mouse spleen: follicular dendritic cells versus capsule and trabeculae. Lötscher, M., Recher, M., Hunziker, L., Klein, M.A. J. Immunol. (2003) [Pubmed]
  15. Intact B cell tolerance in the absence of the first component of the classical complement pathway. Cutler, A.J., Cornall, R.J., Ferry, H., Manderson, A.P., Botto, M., Walport, M.J. Eur. J. Immunol. (2001) [Pubmed]
  16. The innate mononuclear phagocyte network depletes B lymphocytes through Fc receptor-dependent mechanisms during anti-CD20 antibody immunotherapy. Uchida, J., Hamaguchi, Y., Oliver, J.A., Ravetch, J.V., Poe, J.C., Haas, K.M., Tedder, T.F. J. Exp. Med. (2004) [Pubmed]
  17. Novel collectin/C1q receptor mediates mast cell activation and innate immunity. Edelson, B.T., Stricker, T.P., Li, Z., Dickeson, S.K., Shepherd, V.L., Santoro, S.A., Zutter, M.M. Blood (2006) [Pubmed]
  18. Addition of a mu-tailpiece to IgG results in polymeric antibodies with enhanced effector functions including complement-mediated cytolysis by IgG4. Smith, R.I., Coloma, M.J., Morrison, S.L. J. Immunol. (1995) [Pubmed]
  19. Residue at position 331 in the IgG1 and IgG4 CH2 domains contributes to their differential ability to bind and activate complement. Xu, Y., Oomen, R., Klein, M.H. J. Biol. Chem. (1994) [Pubmed]
  20. Complement protein C1q recognizes a conformationally modified form of the prion protein. Blanquet-Grossard, F., Thielens, N.M., Vendrely, C., Jamin, M., Arlaud, G.J. Biochemistry (2005) [Pubmed]
  21. Characterisation of the rat and mouse homologues of gC1qBP, a 33 kDa glycoprotein that binds to the globular 'heads' of C1q. Lynch, N.J., Reid, K.B., van den Berg, R.H., Daha, M.R., Leigh, L.A., Ghebrehiwet, B., Lim, W.B., Schwaeble, W.J. FEBS Lett. (1997) [Pubmed]
  22. Lysine 322 in the human IgG3 C(H)2 domain is crucial for antibody dependent complement activation. Thommesen, J.E., Michaelsen, T.E., Løset GA, n.u.l.l., Sandlie, I., Brekke, O.H. Mol. Immunol. (2000) [Pubmed]
  23. Complement activation contributes to both glomerular and tubulointerstitial damage in adriamycin nephropathy in mice. Turnberg, D., Lewis, M., Moss, J., Xu, Y., Botto, M., Cook, H.T. J. Immunol. (2006) [Pubmed]
  24. Molecular basis of complement resistance of human melanoma cells expressing the C3-cleaving membrane protease p65. Ollert, M.W., Kadlec, J.V., Petrella, E.C., Bredehorst, R., Vogel, C.W. Cancer Res. (1993) [Pubmed]
  25. Activation of human microglia by fibrillar prion protein-related peptides is enhanced by amyloid-associated factors SAP and C1q. Veerhuis, R., Boshuizen, R.S., Morbin, M., Mazzoleni, G., Hoozemans, J.J., Langedijk, J.P., Tagliavini, F., Langeveld, J.P., Eikelenboom, P. Neurobiol. Dis. (2005) [Pubmed]
  26. Involvement of the lectin pathway of complement activation in antimicrobial immune defense during experimental septic peritonitis. Windbichler, M., Echtenacher, B., Hehlgans, T., Jensenius, J.C., Schwaeble, W., Männel, D.N. Infect. Immun. (2004) [Pubmed]
  27. Central role of complement in passive protection by human IgG1 and IgG2 anti-pneumococcal antibodies in mice. Saeland, E., Vidarsson, G., Leusen, J.H., Van Garderen, E., Nahm, M.H., Vile-Weekhout, H., Walraven, V., Stemerding, A.M., Verbeek, J.S., Rijkers, G.T., Kuis, W., Sanders, E.A., Van De Winkel, J.G. J. Immunol. (2003) [Pubmed]
  28. Gene expression of the A- and B-chain of mouse C1q in different tissues and the characterization of the recombinant A-chain. Petry, F., Reid, K.B., Loos, M. J. Immunol. (1991) [Pubmed]
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