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Cited by 320Connective tissue disorders researchCerebrovascular and genetic disordersRenal Diseases and Glomerulopathies

COL4A1 and COL4A2 mutations and disease: insights into pathogenic mechanisms and potential therapeutic targets

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Kuo, D. S., Labelle-Dumais, C., Gould, D. B.·2012·Human Molecular Genetics
DOI 10.1093/hmg/dds346PMC PMC3459649
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Abstract

Heterotrimers composed of collagen type IV alpha 1 (COL4A1) and alpha 2 (COL4A2) constitute one of the most abundant components of nearly all basement membranes. Accordingly, mutations in COL4A1 or COL4A2 are pleiotropic and contribute to a broad spectrum of disorders, including myopathy, glaucoma and hemorrhagic stroke. Here, we summarize the contributions of COL4A1 and COL4A2 mutations in human disease, integrate knowledge gained from model organisms and evaluate the implications for pathogenic mechanisms and therapeutic approaches.

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  • Col4a1 knockout mice develop fragile vessels that are prone to hemorrhage upon hemodynamic stress and mild trauma.

    “Col4a1 knockout mice develop also fragile vessels that are prone to hemorrhage upon hemodynamic stress and mild trauma (337).”

    From Blood-Brain Barrier: From Physiology to Disease and Back (2019) · cites this paper as [337]

    The section on mouse phenotypes (page unavailable) says mice completely deficient for Col4a1 and Col4a2 die at mid-gestation, while the mice reported to have recurrent intracerebral hemorrhages carry a heterozygous Col4a1 mutation—not a knockout. The section on human disease discusses trauma-triggered hemorrhage in patients, not knockout mice; the cited copy does not establish hemodynamic stress as a trigger in those mice. (LLM, conf=0.86)

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  1. [1]Sado Y. Kagawa M. Kishiro Y. Sugihara K. Naito I. Seyer J.M. Sugimoto M. Oohashi T. Ninomiya Y. Establishment by the rat lymph node method of epitope-defined monoclonal antibodies recognizing the six different alpha chains of human type IV collagen Histochem. Cell Biol. 1995 104 267 275 8548560
  2. [2]Borza D.B. Bondar O. Ninomiya Y. Sado Y. Naito I. Todd P. Hudson B.G. The NC1 domain of collagen IV encodes a novel network composed of the alpha 1, alpha 2, alpha 5, and alpha 6 chains in smooth muscle basement membranes J. Biol. Chem. 2001 276 28532 28540 11375996
  3. [3]Boutaud A. Borza D.B. Bondar O. Gunwar S. Netzer K.O. Singh N. Ninomiya Y. Sado Y. Noelken M.E. Hudson B.G. Type IV collagen of the glomerular basement membrane. Evidence that the chain specificity of network assembly is encoded by the noncollagenous NC1 domains J. Biol. Chem. 2000 275 30716 30724 10896941
  4. [4]Gunwar S. Ballester F. Noelken M.E. Sado Y. Ninomiya Y. Hudson B.G. Glomerular basement membrane. Identification of a novel disulfide-cross-linked network of alpha3, alpha4, and alpha5 chains of type IV collagen and its implications for the pathogenesis of Alport syndrome J. Biol. Chem. 1998 273 8767 8775 9535854
  5. [5]Hudson B.G. Tryggvason K. Sundaramoorthy M. Neilson E.G. Alport's syndrome, Goodpasture's syndrome, and type IV collagen N. Engl. J. Med. 2003 348 2543 2556 12815141
  6. [6]Zhou J. Mochizuki T. Smeets H. Antignac C. Laurila P. De Paepe A. Tryggvason K. Reeders S.T. Deletion of the paired alpha 5(IV) and alpha 6(IV) collagen genes in inherited smooth muscle tumors Science 1993 261 1167 1169 8356449
  7. [7]Haniel A. Welge-Lüssen U. Kühn K. Poschl E. Identification and characterization of a novel transcriptional silencer in the human collagen type IV gene COL4A2 J. Biol. Chem. 1995 270 11209 11215 7744753
  8. [8]Burbelo P.D. Martin G.R. Yamada Y. Alpha 1(IV) and alpha 2(IV) collagen genes are regulated by a bidirectional promoter and a shared enhancer Proc. Natl Acad. Sci. USA 1988 85 9679 9682 3200851 PMC282835
  9. [9]Killen P.D. Burbelo P.D. Martin G.R. Yamada Y. Characterization of the promoter for the alpha 1 (IV) collagen gene. DNA sequences within the first intron enhance transcription J. Biol. Chem. 1988 263 12310 12314 2842328
  10. [10]Du B. Ma L.-M. Huang M.-B. Zhou H. Huang H.-L. Shao P. Chen Y.-Q. Qu L.-H. High glucose down-regulates miR-29a to increase collagen IV production in HK-2 cells FEBS Lett. 2010 584 811 816 20067797
  11. [11]Li Z. Hassan M.Q. Jafferji M. Aqeilan R.I. Garzon R. Croce C.M. van Wijnen A.J. Stein J.L. Stein G.S. Lian J.B. Biological functions of miR-29b contribute to positive regulation of osteoblast differentiation J. Biol. Chem. 2009 284 15676 15684 19342382 PMC2708864
  12. [12]Liu Y. Taylor N.E. Lu L. Usa K. Cowley A.W. Ferreri N.R. Yeo N.C. Liang M. Renal medullary micrornas in Dahl salt-sensitive rats: miR-29b regulates several collagens and related genes Hypertension 2010 55 974 982 20194304 PMC2862728
  13. [13]Luna C. Li G. Qiu J. Epstein D.L. Gonzalez P. Role of miR-29b on the regulation of the extracellular matrix in human trabecular meshwork cells under chronic oxidative stress Mol. Vis. 2009 15 2488 2497 19956414 PMC2786891
  14. [14]Maurer B. Stanczyk J. Jüngel A. Akhmetshina A. Trenkmann M. Brock M. Kowal-Bielecka O. Gay R.E. Michel B.A. Distler J.H.W. MicroRNA-29, a key regulator of collagen expression in systemic sclerosis Arthritis Rheum. 2010 62 1733 1743 20201077
  15. [15]Sengupta S. den Boon J.A. Chen I.-H. Newton M.A. Stanhope S.A. Cheng Y.-J. Chen C.-J. Hildesheim A. Sugden B. Ahlquist P. MicroRNA 29c is down-regulated in nasopharyngeal carcinomas, up-regulating mRNAs encoding extracellular matrix proteins Proc. Natl Acad. Sci. USA 2008 105 5874 5878 18390668 PMC2311339
  16. [16]Steele R. Mott J.L. Ray R.B. MBP-1 upregulates miR-29b that represses Mcl-1, collagens, and matrix-metalloproteinase-2 in prostate cancer cells Genes Cancer 2010 1 381 387 20657750 PMC2908325
  17. [17]Kato M. Wang L. Putta S. Wang M. Yuan H. Sun G. Lanting L. Todorov I. Rossi J.J. Natarajan R. Post-transcriptional up-regulation of Tsc-22 by Ybx1, a target of miR-216a, mediates TFG-β-induced collagen expression in kidney cells J. Biol. Chem. 2010 285 34004 34015 20713358 PMC2962500
  18. [18]Chung A.C.K. Huang X.R. Meng X. Lan H.Y. miR-192 mediates TGF-beta/Smad3-driven renal fibrosis J. Am. Soc. Nephrol. 2010 21 1317 1325 20488955 PMC2938591
  19. [19]Sibley M.H. Johnson J.J. Mello C.C. Kramer J.M. Genetic identification, sequence, and alternative splicing of the Caenorhabditis elegans alpha 2(IV) collagen gene J. Cell Biol. 1993 123 255 264 7691828 PMC2119826
  20. [20]Parkin J.D. San Antonio J.D. Pedchenko V. Hudson B. Jensen S.T. Savige J. Mapping structural landmarks, ligand binding sites, and missense mutations to the collagen IV heterotrimers predicts major functional domains, novel interactions, and variation in phenotypes in inherited diseases affecting basement membranes Hum. Mutat. 2011 32 127 143 21280145 PMC4800984
  21. [21]Hofmann H. Voss T. Kühn K. Engel J. Localization of flexible sites in thread-like molecules from electron micrographs. Comparison of interstitial, basement membrane and intima collagens J. Mol. Biol. 1984 172 325 343 6694213
  22. [22]Trüeb B. Gröbli B. Spiess M. Odermatt B.F. Winterhalter K.H. Basement membrane (type IV) collagen is a heteropolymer J. Biol. Chem. 1982 257 5239 5245 6802849
  23. [23]Khoshnoodi J. Cartailler J.-P. Alvares K. Veis A. Hudson B.G. Molecular recognition in the assembly of collagens: terminal noncollagenous domains are key recognition modules in the formation of triple helical protomers J. Biol. Chem. 2006 281 38117 38121 17082192
  24. [24]Winter A.D. Page A.P. Prolyl 4-hydroxylase is an essential procollagen-modifying enzyme required for exoskeleton formation and the maintenance of body shape in the nematode Caenorhabditis elegans Mol. Cell Biol. 2000 20 4084 4093 10805750 PMC85778
  25. [25]Friedman L. Higgin J.J. Moulder G. Barstead R. Raines R.T. Kimble J. Prolyl 4-hydroxylase is required for viability and morphogenesis in Caenorhabditis elegans Proc. Natl Acad. Sci. USA 2000 97 4736 4741 10781079 PMC18302
  26. [26]Holster T. Pakkanen O. Soininen R. Sormunen R. Nokelainen M. Kivirikko K.I. Myllyharju J. Loss of assembly of the main basement membrane collagen, type IV, but not fibril-forming collagens and embryonic death in collagen prolyl 4-hydroxylase I null mice J. Biol. Chem. 2007 282 2512 2519 17135260
  27. [27]Myllyharju J. Prolyl 4-hydroxylases, key enzymes in the synthesis of collagens and regulation of the response to hypoxia, and their roles as treatment targets Ann. Med. 2008 40 402 417 19160570
  28. [28]Vranka J.A. Pokidysheva E. Hayashi L. Zientek K. Mizuno K. Ishikawa Y. Maddox K. Tufa S. Keene D.R. Klein R. Prolyl 3-hydroxylase 1 null mice display abnormalities in fibrillar collagen-rich tissues such as tendons, skin, and bones J. Biol. Chem. 2010 285 17253 17262 20363744 PMC2878055
  29. [29]Tiainen P. Pasanen A. Sormunen R. Myllyharju J. Characterization of recombinant human prolyl 3-hydroxylase isoenzyme 2, an enzyme modifying the basement membrane collagen IV J. Biol. Chem. 2008 283 19432 19439 18487197
  30. [30]Vranka J. Stadler H.S. Bächinger H.P. Expression of prolyl 3-hydroxylase genes in embryonic and adult mouse tissues Cell Struct. Funct. 2009 34 97 104 19652424
  31. [31]Mordechai S. Gradstein L. Pasanen A. Ofir R. El Amour K. Levy J. Belfair N. Lifshitz T. Joshua S. Narkis G. High myopia caused by a mutation in LEPREL1, encoding prolyl 3-hydroxylase 2 Am. J. Hum. Genet. 2011 89 438 445 21885030 PMC3169819
  32. [32]Gorres K.L. Raines R.T. Prolyl 4-hydroxylase Crit. Rev. Biochem. Mol. Biol. 2010 45 106 124 20199358 PMC2841224
  33. [33]Vranka J.A. Sakai L.Y. Bächinger H.P. Prolyl 3-hydroxylase 1, enzyme characterization and identification of a novel family of enzymes J. Biol. Chem. 2004 279 23615 23621 15044469
  34. [34]Hautala T. Heikkinen J. Kivirikko K. A large duplication in the gene for lysyl hydroxylase accounts for the type VI variant of Ehlers-Danlos syndrome in two siblings Genomics 1993 15 399 404 8449506
  35. [35]Pinnell S.R. Krane S.M. Kenzora J.E. Glimcher M.J. A heritable disorder of connective tissue. Hydroxylysine-deficient collagen disease N. Engl. J. Med. 1972 286 1013 1020 5016372
  36. [36]van der Slot A.J. Zuurmond A.M. Bardoel A.F.J. Wijmenga C. Pruijs H.E.H. Sillence D.O. Brinckmann J. Abraham D.J. Black C.M. Verzijl N. Identification of PLOD2 as telopeptide lysyl hydroxylase, an important enzyme in fibrosis J. Biol. Chem. 2003 278 40967 40972 12881513
  37. [37]Salo A.M. Cox H. Farndon P. Moss C. Grindulis H. Risteli M. Robins S.P. Myllylä R. A connective tissue disorder caused by mutations of the lysyl hydroxylase 3 gene Am. J. Hum. Genet. 2008 83 495 503 18834968 PMC2561927
  38. [38]Salo A.M. Wang C. Sipilä L. Sormunen R. Vapola M. Kervinen P. Ruotsalainen H. Heikkinen J. Myllylä R. Lysyl hydroxylase 3 (LH3) modifies proteins in the extracellular space, a novel mechanism for matrix remodeling J. Cell. Physiol. 2006 207 644 653 16447251
  39. [39]Wang C. Ristiluoma M.-M. Salo A.M. Eskelinen S. Myllylä R. Lysyl hydroxylase 3 is secreted from cells by two pathways J. Cell Physiol. 2012 227 668 675 21465473
  40. [40]Heikkinen J. Risteli M. Wang C. Latvala J. Rossi M. Valtavaara M. Myllylä R. Lysyl hydroxylase 3 is a multifunctional protein possessing collagen glucosyltransferase activity J. Biol. Chem. 2000 275 36158 36163 10934207
  41. [41]Rautavuoma K. Takaluoma K. Sormunen R. Myllyharju J. Kivirikko K.I. Soininen R. Premature aggregation of type IV collagen and early lethality in lysyl hydroxylase 3 null mice Proc. Natl Acad. Sci. USA 2004 101 14120 14125 15377789 PMC521128
  42. [42]Norman K.R. Moerman D.G. The Let-268 locus of Caenorhabditis elegans encodes a procollagen lysyl hydroxylase that is essential for type IV collagen secretion Dev. Biol. 2000 227 690 705 11071784
  43. [43]Ruotsalainen H. Sipilä L. Vapola M. Sormunen R. Salo A.M. Uitto L. Mercer D.K. Robins S.P. Risteli M. Aszodi A. Glycosylation catalyzed by lysyl hydroxylase 3 is essential for basement membranes J. Cell Sci. 2006 119 625 635 16467571
  44. [44]Sipilä L. Ruotsalainen H. Sormunen R. Baker N.L. Lamandé S.R. Vapola M. Wang C. Sado Y. Aszodi A. Myllylä R. Secretion and assembly of type IV and VI collagens depend on glycosylation of hydroxylysines J. Biol. Chem. 2007 282 33381 33388 17873278
  45. [45]Ishida Y. Nagata K. Hsp47 as a collagen-specific molecular chaperone Meth. Enzymol. 2011 499 167 182 21683254
  46. [46]Tasab M. Batten M.R. Bulleid N.J. Hsp47: a molecular chaperone that interacts with and stabilizes correctly-folded procollagen EMBO J. 2000 19 2204 2211 10811611 PMC384358
  47. [47]Tasab M. Jenkinson L. Bulleid N.J. Sequence-specific recognition of collagen triple helices by the collagen-specific molecular chaperone HSP47 J. Biol. Chem. 2002 277 35007 35012 12114508
  48. [48]Dafforn T.R. Della M. Miller A.D. The molecular interactions of heat shock protein 47 (Hsp47) and their implications for collagen biosynthesis J. Biol. Chem. 2001 276 49310 49319 11592970
  49. [49]Koide T. Nishikawa Y. Asada S. Yamazaki C.M. Takahara Y. Homma D.L. Otaka A. Ohtani K. Wakamiya N. Nagata K. Specific recognition of the collagen triple helix by chaperone Hsp47. II. The Hsp47-binding structural motif in collagens and related proteins J. Biol. Chem. 2006 281 11177 11185 16484215
  50. [50]Koide T. Takahara Y. Asada S. Nagata K. Xaa-Arg-Gly triplets in the collagen triple helix are dominant binding sites for the molecular chaperone HSP47 J. Biol. Chem. 2002 277 6178 6182 11751879
  51. [51]Nagai N. Hosokawa M. Itohara S. Adachi E. Matsushita T. Hosokawa N. Nagata K. Embryonic lethality of molecular chaperone hsp47 knockout mice is associated with defects in collagen biosynthesis J. Cell Biol. 2000 150 1499 1506 10995453 PMC2150697
  52. [52]Matsuoka Y. Kubota H. Adachi E. Nagai N. Marutani T. Hosokawa N. Nagata K. Insufficient folding of type IV collagen and formation of abnormal basement membrane-like structure in embryoid bodies derived from Hsp47-null embryonic stem cells Mol. Biol. Cell 2004 15 4467 4475 15282337 PMC519141
  53. [53]Marutani T. Yamamoto A. Nagai N. Kubota H. Nagata K. Accumulation of type IV collagen in dilated ER leads to apoptosis in Hsp47-knockout mouse embryos via induction of CHOP J. Cell Sci. 2004 117 5913 5922 15522896
  54. [54]Christiansen H.E. Schwarze U. Pyott S.M. AlSwaid A. Al Balwi M. Alrasheed S. Pepin M.G. Weis M.A. Eyre D.R. Byers P.H. Homozygosity for a missense mutation in SERPINH1, which encodes the collagen chaperone protein HSP47, results in severe recessive Osteogenesis imperfecta Am. J. Hum. Genet. 2010 86 389 398 20188343 PMC2833387
  55. [55]Sasaki T. Hohenester E. Göhring W. Timpl R. Crystal structure and mapping by site-directed mutagenesis of the collagen-binding epitope of an activated form of BM-40/SPARC/osteonectin EMBO J. 1998 17 1625 1634 9501084 PMC1170510
  56. [56]Yan Q. Perdue N. Blake D. Sage E.H. Absence of SPARC in murine lens epithelium leads to increased deposition of laminin-1 in lens capsule Invest. Ophthalmol. Vis. Sci. 2005 46 4652 4660 16303962
  57. [57]Yan Q. Clark J.I. Wight T.N. Sage E.H. Alterations in the lens capsule contribute to cataractogenesis in SPARC-null mice J. Cell Sci. 2002 115 2747 2756 12077365
  58. [58]Norose K. Lo W.K. Clark J.I. Sage E.H. Howe C.C. Lenses of SPARC-null mice exhibit an abnormal cell surface-basement membrane interface Exp. Eye Res. 2000 71 295 307 10973738
  59. [59]Gilmour D.T. Lyon G.J. Carlton M.B. Sanes J.R. Cunningham J.M. Anderson J.R. Hogan B.L. Evans M.J. Colledge W.H. Mice deficient for the secreted glycoprotein SPARC/osteonectin/BM40 develop normally but show severe age-onset cataract formation and disruption of the lens EMBO J. 1998 17 1860 1870 9524110 PMC1170533
  60. [60]Delany A.M. Amling M. Priemel M. Howe C. Baron R. Canalis E. Osteopenia and decreased bone formation in osteonectin-deficient mice J. Clin. Invest. 2000 105 915 923 10749571 PMC377474
  61. [61]Hohenester E. Sasaki T. Giudici C. Farndale R.W. Bächinger H.P. Structural basis of sequence-specific collagen recognition by SPARC Proc. Natl Acad. Sci. USA 2008 105 18273 18277 19011090 PMC2587565
  62. [62]Martinek N. Shahab J. Saathoff M. Ringuette M. Haemocyte-derived SPARC is required for collagen-IV-dependent stability of basal laminae in Drosophila embryos J. Cell Sci. 2008 121 1671 1680 18445681
  63. [63]Fatemi S.H. The role of secretory granules in the transport of basement membrane components: radioautographic studies of rat parietal yolk sac employing 3H-proline as a precursor of type IV collagen Connect. Tissue Res. 1987 16 1 14 2952444
  64. [64]Than M.E. Henrich S. Huber R. Ries A. Mann K. Kühn K. Timpl R. Bourenkov G.P. Bartunik H.D. Bode W. The 1.9-A crystal structure of the noncollagenous (NC1) domain of human placenta collagen IV shows stabilization via a novel type of covalent Met-Lys cross-link Proc. Natl Acad. Sci. USA 2002 99 6607 6612 12011424 PMC124450
  65. [65]Bignon M. Pichol-Thievend C. Hardouin J. Malbouyres M. Bréchot N. Nasciutti L. Barret A. Teillon J. Guillon E. Etienne E. Lysyl oxidase-like protein-2 regulates sprouting angiogenesis and type IV collagen assembly in the endothelial basement membrane Blood 2011 118 3979 3989 21835952
  66. [66]Leitinger B. Hohenester E. Mammalian collagen receptors Matrix Biol. 2007 26 146 155 17141492
  67. [67]Bunt S. Hooley C. Hu N. Scahill C. Weavers H. Skaer H. Hemocyte-secreted type IV collagen enhances BMP signaling to guide renal tubule morphogenesis in Drosophila Dev. Cell 2010 19 296 306 20708591 PMC2941037
  68. [68]Wang X. Harris R.E. Bayston L.J. Ashe H.L. Type IV collagens regulate BMP signalling in Drosophila Nature 2008 455 72 77 18701888
  69. [69]Paralkar V.M. Weeks B.S. Yu Y.M. Kleinman H.K. Reddi A.H. Recombinant human bone morphogenetic protein 2B stimulates PC12 cell differentiation: potentiation and binding to type IV collagen J. Cell Biol. 1992 119 1721 1728 1469059 PMC2289768
  70. [70]Paralkar V.M. Vukicevic S. Reddi A.H. Transforming growth factor beta type 1 binds to collagen IV of basement membrane matrix: implications for development Dev. Biol. 1991 143 303 308 1991553
  71. [71]Madri J.A. Pratt B.M. Tucker A.M. Phenotypic modulation of endothelial cells by transforming growth factor-beta depends upon the composition and organization of the extracellular matrix J. Cell Biol. 1988 106 1375 1384 3283153 PMC2115017
  72. [72]Hynes R.O. Cell-matrix adhesion in vascular development J. Thromb. Haemost. 2007 5 Suppl. 1 32 40 17635706
  73. [73]Colorado P.C. Torre A. Kamphaus G. Maeshima Y. Hopfer H. Takahashi K. Volk R. Zamborsky E.D. Herman S. Sarkar P.K. Anti-angiogenic cues from vascular basement membrane collagen Cancer Res. 2000 60 2520 2526 10811134
  74. [74]Kamphaus G.D. Colorado P.C. Panka D.J. Hopfer H. Ramchandran R. Torre A. Maeshima Y. Mier J.W. Sukhatme V.P. Kalluri R. Canstatin, a novel matrix-derived inhibitor of angiogenesis and tumor growth J. Biol. Chem. 2000 275 1209 1215 10625665
  75. [75]Nyberg P. Xie L. Sugimoto H. Colorado P. Sund M. Holthaus K. Sudhakar A. Salo T. Kalluri R. Characterization of the anti-angiogenic properties of arresten, an α1β1 integrin-dependent collagen-derived tumor suppressor Exp. Cell Res. 2008 314 3292 3305 18775695 PMC2613512
  76. [76]Sudhakar A. Boosani C.S. Signaling mechanisms of endogenous angiogenesis inhibitors derived from type IV collagen Gene Regul. Syst. Biol. 2007 1 217 226 PMC2759143 19936090
  77. [78]Sund M. Hamano Y. Sugimoto H. Sudhakar A. Soubasakos M. Yerramalla U. Benjamin L.E. Lawler J. Kieran M. Shah A. Function of endogenous inhibitors of angiogenesis as endothelium-specific tumor suppressors Proc. Natl Acad. Sci. USA 2005 102 2934 2939 15710885 PMC549486
  78. [79]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.M. Mutations in Col4a1 cause perinatal cerebral hemorrhage and porencephaly Science 2005 308 1167 1171 15905400
  79. [80]Gould D.B. Phalan F.C. van Mil S.E. Sundberg J.P. Vahedi K. Massin P. Bousser M.G. Heutink P. Miner J.H. Tournier-Lasserve E. Role of COL4A1 in small-vessel disease and hemorrhagic stroke N. Engl. J. Med. 2006 354 1489 1496 16598045
  80. [81]Breedveld G. de Coo I.F. Lequin M.H. Arts W.F.M. Heutink P. Gould D.B. John S.W.M. Oostra B. Mancini G.M.S. Novel mutations in three families confirm a major role of COL4A1 in hereditary porencephaly J. Med. Genet. 2006 43 490 495 16107487 PMC2593028
  81. [82]Vahedi K. Kubis N. Boukobza M. Arnoult M. Massin P. Tournier-Lasserve E. Bousser M.G. COL4A1 mutation in a patient with sporadic, recurrent intracerebral hemorrhage Stroke 2007 38 1461 1464 17379824
  82. [83]Lichtenbelt K.D. Pistorius L.R. de Tollenaer S.M. Mancini G.M. de Vries L.S. Prenatal genetic confirmation of a COL4A1 mutation presenting with sonographic fetal intracranial hemorrhage Ultrasound Obstet. Gynecol. 2012 39 726 727 22223490
  83. [84]Weng Y.-C. Sonni A. Labelle-Dumais C. De Leau M. Kauffman W.B. Jeanne M. Biffi A. Greenberg S.M. Rosand J. Gould D.B. COL4A1 mutations in patients with sporadic late-onset intracerebral hemorrhage Ann. Neurol. 2012 71 470 477 22522439 PMC3335762
  84. [85]Jeanne M. Labelle-Dumais C. Jorgensen J. Kauffman W.B. Mancini G.M. Favor J. Valant V. Greenberg S.M. Rosand J. Gould D.B. COL4A2 mutations impair COL4A1 and COL4A2 secretion and cause hemorrhagic stroke Am. J. Hum. Genet. 2012 90 91 101 22209247 PMC3257894
  85. [86]Verbeek E. Meuwissen M.E. Verheijen F.W. Govaert P.P. Licht D.J. Kuo D.S. Poulton C.J. Schot R. Lequin M.H. Dudink J. COL4A2 mutation associated with familial porencephaly and small-vessel disease Eur. J. Hum. Genet. 2012 20 844 851 22333902 PMC3400734
  86. [87]Yoneda Y. Haginoya K. Arai H. Yamaoka S. Tsurusaki Y. Doi H. Miyake N. Yokochi K. Osaka H. Kato M. De novo and inherited mutations in COL4A2, encoding the type IV collagen α2 chain cause porencephaly Am. J. Hum. Genet. 2012 90 86 90 22209246 PMC3257897
  87. [88]Sibon I. Coupry I. Menegon P. Bouchet J.-P. Gorry P. Burgelin I. Calvas P. Orignac I. Dousset V. Lacombe D. COL4A1 mutation in Axenfeld-Rieger anomaly with leukoencephalopathy and stroke Ann. Neurol. 2007 62 177 184 17696175
  88. [89]Vahedi K. Boukobza M. Massin P. Gould D.B. Tournier-Lasserve E. Bousser M.-G. Clinical and brain MRI follow-up study of a family with COL4A1 mutation Neurology 2007 69 1564 1568 17938367
  89. [90]Plaisier E. Gribouval O. Alamowitch S. Mougenot B. Prost C. Verpont M.C. Marro B. Desmettre T. Cohen S.Y. Roullet E. COL4A1 mutations and hereditary angiopathy, nephropathy, aneurysms, and muscle cramps N. Engl. J. Med. 2007 357 2687 2695 18160688
  90. [91]Alamowitch S. Plaisier E. Favrole P. Prost C. Chen Z. Van Agtmael T. Marro B. Ronco P. Cerebrovascular disease related to COL4A1 mutations in HANAC syndrome Neurology 2009 73 1873 1882 19949034 PMC2881859
  91. [92]Shah S. Kumar Y. McLean B. Churchill A. Stoodley N. Rankin J. Rizzu P. van der Knaap M. Jardine P. A dominantly inherited mutation in collagen IV A1 (COL4A1) causing childhood onset stroke without porencephaly Eur. J. Paediatr. Neurol. 2010 14 182 187 19477666
  92. [93]Rouaud T. Labauge P. Tournier Lasserve E. Mine M. Coustans M. Deburghgraeve V. Edan G. Acute urinary retention due to a novel collagen COL4A1 mutation Neurology 2010 75 747 749 20733150
  93. [94]Plaisier E. Chen Z. Gekeler F. Benhassine S. Dahan K. Marro B. Alamowitch S. Paques M. Ronco P. Novel COL4A1 mutations associated with HANAC syndrome: a role for the triple helical CB3[IV] domain Am. J. Med. Genet. A 2010 152A 2550 2555 20818663
  94. [95]Livingston J. Doherty D. Orcesi S. Tonduti D. Piechiecchio A. La Piana R. Tournier-Lasserve E. Majumdar A. Tomkins S. Rice G. COL4A1 mutations associated with a characteristic pattern of intracranial calcification Neuropediatrics 2011 42 227 233 22134833
  95. [96]Shah S. Ellard S. Kneen R. Lim M. Osborne N. Rankin J. Stoodley N. van der Knaap M. Whitney A. Jardine P. Childhood presentation of COL4A1 mutations Dev. Med. Child Neurol. 2012 54 569 574 22574627
  96. [97]Labelle-Dumais C. Dilworth D.J. Harrington E.P. De Leau M. Lyons D. Kabaeva Z. Manzini M.C. Dobyns W.B. Walsh C.A. Michele D.E. COL4A1 mutations cause ocular dysgenesis, neuronal localization defects, and myopathy in mice and Walker-Warburg syndrome in humans PLoS Genet. 2011 7 e1002062 21625620 PMC3098190
  97. [98]Pöschl E. Schlötzer-Schrehardt U. Brachvogel B. Saito K. Ninomiya Y. Mayer U. Collagen IV is essential for basement membrane stability but dispensable for initiation of its assembly during early development Development 2004 131 1619 1628 14998921
  98. [99]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. Dominant mutations of Col4a1 result in basement membrane defects which lead to anterior segment dysgenesis and glomerulopathy Hum. Mol. Genet. 2005 14 3161 3168 16159887
  99. [100]Favor J. Gloeckner C.J. Janik D. Klempt M. Neuhäuser-Klaus A. Pretsch W. Schmahl W. Quintanilla-Fend L. Type IV procollagen missense mutations associated with defects of the eye, vascular stability, the brain, kidney function and embryonic or postnatal viability in the mouse, Mus musculus: an extension of the Col4a1 allelic series and the identification of the first two Col4a2 mutant alleles Genetics 2007 175 725 736 17179069 PMC1800636
  100. [101]Gould D.B. Marchant J.K. Savinova O.V. Smith R.S. John S.W.M. Col4a1 mutation causes endoplasmic reticulum stress and genetically modifiable ocular dysgenesis Hum. Mol. Genet. 2007 16 798 807 17317786
  101. [102]Van Agtmael T. Bailey M.A. Schlötzer-Schrehardt U. Craigie E. Jackson I.J. Brownstein D.G. Megson I.L. Mullins J.J. Col4a1 mutation in mice causes defects in vascular function and low blood pressure associated with reduced red blood cell volume Hum. Mol. Genet. 2010 19 1119 1128 20056676 PMC3199583
  102. [103]Fox M.A. Sanes J.R. Borza D.-B. Eswarakumar V.P. Fässler R. Hudson B.G. John S.W.M. Ninomiya Y. Pedchenko V. Pfaff S.L. Distinct target-derived signals organize formation, maturation, and maintenance of motor nerve terminals Cell 2007 129 179 193 17418794
  103. [104]Kelemen-Valkony I. Kiss M. Csiha J. Kiss A. Bircher U. Szidonya J. Maróy P. Juhász G. Komonyi O. Csiszár K. Drosophila basement membrane collagen Col4a1 mutations cause severe myopathy Matrix Biol. 2012 31 29 37 22037604
  104. [105]Firtina Z. Danysh B.P. Bai X. Gould D.B. Kobayashi T. Duncan M.K. Abnormal expression of collagen IV in lens activates unfolded protein response resulting in cataract J. Biol. Chem. 2009 284 35872 35884 19858219 PMC2791016
  105. [106]Goumans M.-J. Liu Z. ten Dijke P. TGF-β signaling in vascular biology and dysfunction Cell Res. 2009 19 116 127 19114994
  106. [107]Habashi J.P. Judge D.P. Holm T.M. Cohn R.D. Loeys B.L. Cooper T.K. Myers L. Klein E.C. Liu G. Calvi C. Losartan, an AT1 antagonist, prevents aortic aneurysm in a mouse model of Marfan syndrome Science 2006 312 117 121 16601194 PMC1482474
  107. [108]Neptune E.R. Frischmeyer P.A. Arking D.E. Myers L. Bunton T.E. Gayraud B. Ramirez F. Sakai L.Y. Dietz H.C. Dysregulation of TGF-β activation contributes to pathogenesis in Marfan syndrome Nat. Genet. 2003 33 407 411 12598898
  108. [109]Prockop D.J. Kivirikko K.I. Collagens: molecular biology, diseases, and potentials for therapy Annu. Rev. Biochem. 1995 64 403 434 7574488
  109. [110]Baker N.L. Mörgelin M. Pace R.A. Peat R.A. Adams N.E. Gardner R.J.M. Rowland L.P. Miller G. De Jonghe P. Ceulemans B. Molecular consequences of dominant Bethlem myopathy collagen VI mutations Ann. Neurol. 2007 62 390 405 17886299
  110. [111]Gelman M.S. Kannegaard E.S. Kopito R.R. A principal role for the proteasome in endoplasmic reticulum-associated degradation of misfolded intracellular cystic fibrosis transmembrane conductance regulator J. Biol. Chem. 2002 277 11709 11714 11812794
  111. [112]Ishida Y. Kubota H. Yamamoto A. Kitamura A. Bächinger H.P. Nagata K. Type I collagen in Hsp47-null cells is aggregated in endoplasmic reticulum and deficient in N-propeptide processing and fibrillogenesis Mol. Biol. Cell 2006 17 2346 2355 16525016 PMC1446091
  112. [113]Ishida Y. Nagata K. Autophagy eliminates a specific species of misfolded procollagen and plays a protective role in cell survival against ER stress Autophagy 2009 5 1217 1219 19829057
  113. [114]Pan T. Kondo S. Le W. Jankovic J. The role of autophagy-lysosome pathway in neurodegeneration associated with Parkinson's disease Brain 2008 131 1969 1978 18187492
  114. [115]Zhang L. Yu J. Pan H. Hu P. Hao Y. Cai W. Zhu H. Yu A.D. Xie X. Ma D. Small molecule regulators of autophagy identified by an image-based high-throughput screen Proc. Natl Acad. Sci. USA 2007 104 19023 19028 18024584 PMC2141901
  115. [116]Gupta M.C. Graham P.L. Kramer J.M. Characterization of α1(IV) collagen mutations in Caenorhabditis elegans and the effects of α1 and α2(IV) mutations on type IV collagen distribution J. Cell Biol. 1997 137 1185 1196 9166417 PMC2136222
  116. [117]Welch W.J. Brown C.R. Influence of molecular and chemical chaperones on protein folding Cell Stress Chaperon. 1996 1 109 115 PMC248462 9222596
  117. [118]de Almeida S.F. Picarote G. Fleming J.V. Carmo-Fonseca M. Azevedo J.E. de Sousa M. Chemical chaperones reduce endoplasmic reticulum stress and prevent mutant HFE aggregate formation J. Biol. Chem. 2007 282 27905 27912 17626021
  118. [119]Bonapace G. Waheed A. Shah G.N. Sly W.S. Chemical chaperones protect from effects of apoptosis-inducing mutation in carbonic anhydrase IV identified in retinitis pigmentosa 17 Proc. Natl Acad. Sci. USA 2004 101 12300 12305 15295099 PMC514473
  119. [120]Brown C.R. Hong-Brown L.Q. Biwersi J. Verkman A.S. Welch W.J. Chemical chaperones correct the mutant phenotype of the Delta F508 cystic fibrosis transmembrane conductance regulator protein Cell Stress Chaperon 1996 1 117 125 PMC248464 9222597
  120. [121]Malhotra J.D. Miao H. Zhang K. Wolfson A. Pennathur S. Pipe S.W. Kaufman R.J. Antioxidants reduce endoplasmic reticulum stress and improve protein secretion Proc. Natl Acad. Sci. USA 2008 105 18525 18530 19011102 PMC2587584
  121. [122]Yam G.H.-F. Gaplovska-Kysela K. Zuber C. Roth J. Sodium 4-phenylbutyrate acts as a chemical chaperone on misfolded myocilin to rescue cells from endoplasmic reticulum stress and apoptosis Invest. Ophthalmol. Vis. Sci. 2007 48 1683 1690 17389500
  122. [123]Aguglia U. Gambardella A. Breedveld G.J. Oliveri R.L. Le Paine E. Messina D. Quattrone A. Heutink P. Suggestive evidence for linkage to chromosome 13qter for autosomal dominant type 1 porencephaly Neurology 2004 62 1613 1615 15136694
  123. [124]Vermeulen R.J. Peeters-Scholte C. Van Vugt J.J.M. Van Vught J.J.M.G. Barkhof F. Rizzu P. van der Schoor S.R.D. van der Knaap M.S. Fetal origin of brain damage in 2 infants with a Col4a1 mutation: fetal and neonatal MRI Neuropediatrics 2011 42 1 3 21500141
  124. [125]Meuwissen M.E.C. de Vries L.S. Verbeek H.A. Lequin M.H. Govaert P.P. Schot R. Cowan F.M. Hennekam R. Rizzu P. Verheijen F.W. Sporadic Col4a1 mutations with extensive prenatal porencephaly resembling hydranencephaly Neurology 2011 76 844 846 21357838
  125. [126]van der Knaap M.S. Smit L.M.E. Barkhof F. Pijnenburg Y.A.L. Zweegman S. Niessen H.W.M. Imhof S. Heutink P. Neonatal porencephaly and adult stroke related to mutations in Collagen IV A1 Ann. Neurol 2006 59 504 511 16374828
  126. [127]Bilguvar K. DiLuna M.L. Biazzaro M.J. Bayri Y. Schneider K.C. Lifton R.P. Ment L.R. Pacifier, Breastfeeding Trial Group COL4A1 mutation in preterm intraventricular hemorrhage J. Pediatr 2009 155 743 745 19840616 PMC2884156
  127. [128]de Vries L.S. Koopman C. Groenendaal F. Van Schooneveld M. Verheijen F.W. Verbeek E. Witkamp T.D. van der Worp H.B. Mancini G. Col4a1 mutation in two preterm siblings with antenatal onset of parenchymal hemorrhage Ann. Neurol 2009 65 12 18 19194877

Cited by

Sorted by citations

Authors
Kuo, D. S., Labelle-Dumais, C., & Gould, D. B.
Affiliations
University of California, San Francisco (US)
Corresponding author
Gould, D. B.
ORCID
Venue
Human Molecular Genetics
Publisher
Oxford University Press (OUP)
Published
2012-08-21
Volume
21
Issue
R1
Pages
R97-R110
ISSN
  • 0964-6906 (ISSN-L)
  • 1460-2083
DOI
10.1093/hmg/dds346
PMC
PMC3459649
OpenAlex
W2162695141
Cited by
320
References
1
Citations by year
2026: 18 · 2025: 30 · 2024: 36 · 2023: 26 · 2022: 34 · 2021: 22 · 2020: 19 · 2019: 24 · 2018: 18 · 2017: 14 · 2016: 21 · 2015: 24 · 2014: 21 · 2013: 6
FWCI
1.99
Type
journal article
Language
en
Open access
Licence
other-oa
Locations
  • Human Molecular Genetics (publishedVersion, other-oa)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
  • eScholarship (California Digital Library) (submittedVersion)
Funders
  • Howard Hughes Medical Institute
  • American Heart Association
  • Research to Prevent Blindness
  • Muscular Dystrophy Association
  • That Man May See
  • National Institutes of Health
  • National Eye Institute (P30EY002162, R01EY019514, R01EY019887)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Connective tissue disorders research
  • Health Sciences › Medicine › Neurology › Cerebrovascular and genetic disorders
  • Health Sciences › Medicine › Nephrology › Renal Diseases and Glomerulopathies
Keywords
COL4A1, COL4A2, basement membrane, heterotrimers, myopathy, glaucoma, hemorrhagic stroke, pleiotropic mutations, pathophysiological mechanisms, therapeutic target, model organisms
MeSH terms
Animals, Basement Membrane, Biological Transport, Glaucoma, Humans, Muscular Diseases, Mutation, Phenotype, Genetic Predisposition to Disease, Stroke, Collagen Type IV, Mice, Protein Multimerization, Molecular Targeted Therapy

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