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Gene Review

Col4a1  -  collagen, type IV, alpha 1

Mus musculus

Synonyms: Bru, Col4a-1, Collagen alpha-1(IV) chain, Del(8)44H, Del(8)Bru44H, ...
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Disease relevance of Col4a1


High impact information on Col4a1

  • Airway resistance responses (Raw) to the muscarinic agonist methacholine were measured by using the forced oscillation technique [5].
  • (iv) Salbutamol, a beta-AR partial agonist, acutely decreased peak Raw by 41.1%; chronically, it did not alter Raw [5].
  • (iii) Alprenolol, a beta-blocker with partial agonist properties at beta-ARs, behaved as a beta-AR agonist, and acutely reduced peak Raw value by 75.7% (P < 0.05); chronically, it did not alter Raw [5].
  • Dominant mutations of Col4a1 result in basement membrane defects which lead to anterior segment dysgenesis and glomerulopathy [2].
  • We have identified an allelic series of three ENU induced dominant mouse mutants with missense mutations in the gene Col4a1 encoding the alpha1(IV) subunit chain [2].

Biological context of Col4a1

  • To analyze the functional roles of the major collagen IV isoform alpha1(IV)(2)alpha2(IV) for basement membrane assembly and embryonic development, we generated a null allele of the Col4a1/2 locus in mice, thereby ablating both alpha-chains [6].
  • By contrast, Cf10, Col4a1, Col4a2, and D8H13S35 mapped near the centromere of mouse Chr 8, defining a new conserved linkage [7].
  • Differentiating Raw with respect to time revealed a greater rate of bronchoconstriction for the WT during the initial 4 s, presumably reflecting the faster shortening velocities under these relatively unloaded conditions [8].
  • In Raw cells, specific inhibition of gamma-IFN induction of endogenous-C/EBPbeta phosphorylation by MEKK1 markedly reduced basal promoter activity and the response to gamma-IFN [9].

Anatomical context of Col4a1


Associations of Col4a1 with chemical compounds

  • Two severe alleles (Bru and Svc) have mutations affecting the conserved glycine residues in the Gly-Xaa-Yaa collagen repeat [2].
  • Among the extracts, HD-02 efficiently inhibited the production of NO and citrulline, and the expression of inducible NO synthase (iNOS) mRNA by LPS-stimulated mouse macrophage-like cells Raw 264 [15].
  • Transfection experiments expressing human FcgammaRIIbl or b2 in Raw 264.7 murine macrophage cells revealed that both isoforms are tyrosine phosphorylated and promote SHIP phosphorylation [16].
  • METHODS: Mouse macrophages (cell line Raw 264.7) were cultured and incubated with a nitric oxide donor sodium nitroprusside (SNP), PPF, and a combination of PPF and SNP for one, six and 24 hr [17].
  • In contrast, sensitized chronically exposed mice had significantly elevated Raw at all concentrations of Mch but no increases in G, H or eta indicating airway-specific hyperresponsiveness [18].

Other interactions of Col4a1

  • Finally, we identified either a closely linked sequence related to Col4a2, or a recombination hot-spot between Col4a1 and Col4a2 that has been conserved in humans and mice [7].
  • Full-thickness skin wounds were created in mice, and subsequent expression of vascular endothelial growth factor (VEGF), the VEGF receptor Flk-1, alpha1 (iv) collagen (Col4a1), and Sox18 were studied using in situ hybridization [10].
  • In addition, the protein caused the murine macrophage cell line Raw 264.7 to produce cyclooxygenase-2, nitric oxide synthase, nitric oxide, and tumor necrosis factor-alpha [19].
  • A milder allele (Raw) contains a mutation in the Yaa residue of the collagen repeat and was identified by a silvery appearance of the retinal arterioles [2].

Analytical, diagnostic and therapeutic context of Col4a1


  1. Mutations in Col4a1 cause perinatal cerebral hemorrhage and porencephaly. Gould, D.B., Phalan, F.C., Breedveld, G.J., van Mil, S.E., Smith, R.S., Schimenti, J.C., Aguglia, U., van der Knaap, M.S., Heutink, P., John, S.W. Science (2005) [Pubmed]
  2. Dominant mutations of Col4a1 result in basement membrane defects which lead to anterior segment dysgenesis and glomerulopathy. Van Agtmael, T., Schlötzer-Schrehardt, U., McKie, L., Brownstein, D.G., Lee, A.W., Cross, S.H., Sado, Y., Mullins, J.J., Pöschl, E., Jackson, I.J. Hum. Mol. Genet. (2005) [Pubmed]
  3. Resistance to human immunodeficiency virus 1 infection of SCID mice reconstituted with peripheral blood leukocytes from donors vaccinated with vaccinia gp160 and recombinant gp160. Mosier, D.E., Gulizia, R.J., MacIsaac, P.D., Corey, L., Greenberg, P.D. Proc. Natl. Acad. Sci. U.S.A. (1993) [Pubmed]
  4. Continuous propagation of Ehrlichia sennetsu in murine macrophage cell cultures. Cole, A.I., Ristic, M., Lewis, G.E., Rapmund, G. Am. J. Trop. Med. Hyg. (1985) [Pubmed]
  5. Effects of acute and chronic administration of beta-adrenoceptor ligands on airway function in a murine model of asthma. Callaerts-Vegh, Z., Evans, K.L., Dudekula, N., Cuba, D., Knoll, B.J., Callaerts, P.F., Giles, H., Shardonofsky, F.R., Bond, R.A. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
  6. Collagen IV is essential for basement membrane stability but dispensable for initiation of its assembly during early development. Pöschl, E., Schlötzer-Schrehardt, U., Brachvogel, B., Saito, K., Ninomiya, Y., Mayer, U. Development (2004) [Pubmed]
  7. Homologs of genes and anonymous loci on human chromosome 13 map to mouse chromosomes 8 and 14. Koizumi, T., Hendel, E., Lalley, P.A., Tchetgen, M.B., Nadeau, J.H. Mamm. Genome (1995) [Pubmed]
  8. Time course of airway mechanics of the (+)insert myosin isoform knockout mouse. Tuck, S.A., Maghni, K., Poirier, A., Babu, G.J., Periasamy, M., Bates, J.H., Leguillette, R., Lauzon, A.M. Am. J. Respir. Cell Mol. Biol. (2004) [Pubmed]
  9. 1alpha-Hydroxylase transactivation by gamma-interferon in murine macrophages requires enhanced C/EBPbeta expression and activation. Esteban, L., Vidal, M., Dusso, A. J. Steroid Biochem. Mol. Biol. (2004) [Pubmed]
  10. Sox18 is transiently expressed during angiogenesis in granulation tissue of skin wounds with an identical expression pattern to Flk-1 mRNA. Darby, I.A., Bisucci, T., Raghoenath, S., Olsson, J., Muscat, G.E., Koopman, P. Lab. Invest. (2001) [Pubmed]
  11. The ubiquitin-like protein MNSFbeta regulates ERK-MAPK cascade. Nakamura, M., Yamaguchi, S. J. Biol. Chem. (2006) [Pubmed]
  12. Vasoactive intestinal peptide (VIP) inhibits TGF-beta1 production in murine macrophages. Sun, W., Tadmori, I., Yang, L., Delgado, M., Ganea, D. J. Neuroimmunol. (2000) [Pubmed]
  13. Tyrosine phosphorylation of inducible nitric oxide synthase: implications for potential post-translational regulation. Pan, J., Burgher, K.L., Szczepanik, A.M., Ringheim, G.E. Biochem. J. (1996) [Pubmed]
  14. Direct stimulation of macrophages by IL-12 and IL-18--a bridge too far? Gołab, J., Zagozdzon, n.u.l.l., Stokłosal, T., Kamiński, R., Kozar, K., Jakóbisiak, M. Immunol. Lett. (2000) [Pubmed]
  15. Effect of poly-herbal formula on NO production by LPS-stimulated mouse macrophage-like cells. Miyamoto, M., Hashimoto, K., Minagawa, K., Satoh, K., Komatsu, N., Fujimaki, M., Nakashima, H., Yokote, Y., Akahane, K., Guputa, M., Sarma, D.N., Mitra, S.K., Sakagami, H. Anticancer Res. (2002) [Pubmed]
  16. Molecular analysis of expression and function of hFcgammaRIIbl and b2 isoforms in myeloid cells. Joshi, T., Ganesan, L.P., Cao, X., Tridandapani, S. Mol. Immunol. (2006) [Pubmed]
  17. Therapeutic concentrations of propofol protects mouse macrophages from nitric oxide-induced cell death and apoptosis. Chang, H., Tsai, S.Y., Chang, Y., Chen, T.L., Chen, R.M. Canadian journal of anaesthesia = Journal canadien d'anesthésie. (2002) [Pubmed]
  18. Site of inflammation influences site of hyperresponsiveness in experimental asthma. Collins, R.A., Sly, P.D., Turner, D.J., Herbert, C., Kumar, R.K. Respiratory physiology & neurobiology. (2003) [Pubmed]
  19. Anticoagulant from Taraxacum platycarpum. Yun, S.I., Cho, H.R., Choi, H.S. Biosci. Biotechnol. Biochem. (2002) [Pubmed]
  20. IL-10 gene knockout attenuates allergen-induced airway hyperresponsiveness in C57BL/6 mice. Justice, J.P., Shibata, Y., Sur, S., Mustafa, J., Fan, M., Van Scott, M.R. Am. J. Physiol. Lung Cell Mol. Physiol. (2001) [Pubmed]
  21. Lung tissue behavior in the mouse during constriction induced by methacholine and endothelin-1. Nagase, T., Matsui, H., Aoki, T., Ouchi, Y., Fukuchi, Y. J. Appl. Physiol. (1996) [Pubmed]
  22. Geometric determinants of airway resistance in two isomorphic rodent species. Gomes, R.F., Bates, J.H. Respiratory physiology & neurobiology. (2002) [Pubmed]
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