Cellular and Molecular Life Sciences

, Volume 74, Issue 6, pp 1095–1115 | Cite as

Laminin: loss-of-function studies



Laminin, one of the most widely expressed extracellular matrix proteins, exerts many important functions in multiple organs/systems and at various developmental stages. Although its critical roles in embryonic development have been demonstrated, laminin’s functions at later stages remain largely unknown, mainly due to its intrinsic complexity and lack of research tools (most laminin mutants are embryonic lethal). With the advance of genetic and molecular techniques, many new laminin mutants have been generated recently. These new mutants usually have a longer lifespan and show previously unidentified phenotypes. Not only do these studies suggest novel functions of laminin, but also they provide invaluable animal models that allow investigation of laminin’s functions at late stages. Here, I first briefly introduce the nomenclature, structure, and biochemistry of laminin in general. Next, all the loss-of-function mutants/models for each laminin chain are discussed and their phenotypes compared. I hope to provide a comprehensive review on laminin functions and its loss-of-function models, which could serve as a reference for future research in this understudied field.


Laminin Knockout Loss-of-function Animal model Basement membrane 



This work was supported by Myotonic Dystrophy Foundation Fund-A-Fellow Grant (Y.Y.). The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Compliance with ethical standards

Conflict of interest

The author declares no competing interests.


  1. 1.
    Aumailley M, Bruckner-Tuderman L, Carter WG, Deutzmann R, Edgar D, Ekblom P, Engel J, Engvall E, Hohenester E, Jones JC, Kleinman HK, Marinkovich MP, Martin GR, Mayer U, Meneguzzi G, Miner JH, Miyazaki K, Patarroyo M, Paulsson M, Quaranta V, Sanes JR, Sasaki T, Sekiguchi K, Sorokin LM, Talts JF, Tryggvason K, Uitto J, Virtanen I, von der Mark K, Wewer UM, Yamada Y, Yurchenco PD (2005) A simplified laminin nomenclature. Matrix Biol 24(5):326–332. doi: 10.1016/j.matbio.2005.05.006 PubMedCrossRefGoogle Scholar
  2. 2.
    Aumailley M (2013) The laminin family. Cell Adhes Migration 7(1):48–55. doi: 10.4161/cam.22826 CrossRefGoogle Scholar
  3. 3.
    Durbeej M (2010) Laminins. Cell Tissue Res 339(1):259–268. doi: 10.1007/s00441-009-0838-2 PubMedCrossRefGoogle Scholar
  4. 4.
    Burgeson RE, Chiquet M, Deutzmann R, Ekblom P, Engel J, Kleinman H, Martin GR, Meneguzzi G, Paulsson M, Sanes J et al (1994) A new nomenclature for the laminins. Matrix Biol 14(3):209–211PubMedCrossRefGoogle Scholar
  5. 5.
    Ferrigno O, Virolle T, Galliano MF, Chauvin N, Ortonne JP, Meneguzzi G, Aberdam D (1997) Murine laminin alpha3A and alpha3B isoform chains are generated by usage of two promoters and alternative splicing. J Biol Chem 272(33):20502–20507PubMedCrossRefGoogle Scholar
  6. 6.
    Sasaki T, Timpl R (1999) Laminins. In: Kries T, Vale R (eds) Guidebook to the extracellular matrix, anchor, and adhesion proteins. Oxford University Press, Oxford, pp 434–443Google Scholar
  7. 7.
    Maurer P, Engel J (1996) Structure of laminins and their chain assembly. In: Ekblom P, Timpl R (eds) The laminins. Harwood Academic Press, Amsterdam, pp 27–49Google Scholar
  8. 8.
    Miner JH, Yurchenco PD (2004) Laminin functions in tissue morphogenesis. Annu Rev Cell Dev Biol 20:255–284. doi: 10.1146/annurev.cellbio.20.010403.094555 PubMedCrossRefGoogle Scholar
  9. 9.
    Morita A, Sugimoto E, Kitagawa Y (1985) Post-translational assembly and glycosylation of laminin subunits in parietal endoderm-like F9 cells. Biochem J 229(1):259–264PubMedPubMedCentralCrossRefGoogle Scholar
  10. 10.
    Champliaud MF, Virtanen I, Tiger CF, Korhonen M, Burgeson R, Gullberg D (2000) Posttranslational modifications and beta/gamma chain associations of human laminin alpha1 and laminin alpha5 chains: purification of laminin-3 from placenta. Exp Cell Res 259(2):326–335. doi: 10.1006/excr.2000.4980 PubMedCrossRefGoogle Scholar
  11. 11.
    Tzu J, Marinkovich MP (2008) Bridging structure with function: structural, regulatory, and developmental role of laminins. Int J Biochem Cell Biol 40(2):199–214. doi: 10.1016/j.biocel.2007.07.015 PubMedCrossRefGoogle Scholar
  12. 12.
    Schneider H, Muhle C, Pacho F (2007) Biological function of laminin-5 and pathogenic impact of its deficiency. Eur J Cell Biol 86(11–12):701–717. doi: 10.1016/j.ejcb.2006.07.004 PubMedCrossRefGoogle Scholar
  13. 13.
    Yurchenco PD, Wadsworth WG (2004) Assembly and tissue functions of early embryonic laminins and netrins. Curr Opin Cell Biol 16(5):572–579. doi: 10.1016/ PubMedCrossRefGoogle Scholar
  14. 14.
    Kohfeldt E, Sasaki T, Gohring W, Timpl R (1998) Nidogen-2: a new basement membrane protein with diverse binding properties. J Mol Biol 282(1):99–109. doi: 10.1006/jmbi.1998.2004 PubMedCrossRefGoogle Scholar
  15. 15.
    Fox JW, Mayer U, Nischt R, Aumailley M, Reinhardt D, Wiedemann H, Mann K, Timpl R, Krieg T, Engel J et al (1991) Recombinant nidogen consists of three globular domains and mediates binding of laminin to collagen type IV. EMBO J 10(11):3137–3146PubMedPubMedCentralGoogle Scholar
  16. 16.
    Aumailley M, Battaglia C, Mayer U, Reinhardt D, Nischt R, Timpl R, Fox JW (1993) Nidogen mediates the formation of ternary complexes of basement membrane components. Kidney Int 43(1):7–12PubMedCrossRefGoogle Scholar
  17. 17.
    Salmivirta K, Talts JF, Olsson M, Sasaki T, Timpl R, Ekblom P (2002) Binding of mouse nidogen-2 to basement membrane components and cells and its expression in embryonic and adult tissues suggest complementary functions of the two nidogens. Exp Cell Res 279(2):188–201PubMedCrossRefGoogle Scholar
  18. 18.
    Mayer U, Nischt R, Poschl E, Mann K, Fukuda K, Gerl M, Yamada Y, Timpl R (1993) A single EGF-like motif of laminin is responsible for high affinity nidogen binding. EMBO J 12(5):1879–1885PubMedPubMedCentralGoogle Scholar
  19. 19.
    Poschl E, Fox JW, Block D, Mayer U, Timpl R (1994) Two non-contiguous regions contribute to nidogen binding to a single EGF-like motif of the laminin gamma 1 chain. EMBO J 13(16):3741–3747PubMedPubMedCentralGoogle Scholar
  20. 20.
    Poschl E, Mayer U, Stetefeld J, Baumgartner R, Holak TA, Huber R, Timpl R (1996) Site-directed mutagenesis and structural interpretation of the nidogen binding site of the laminin gamma1 chain. EMBO J 15(19):5154–5159PubMedPubMedCentralGoogle Scholar
  21. 21.
    Stetefeld J, Mayer U, Timpl R, Huber R (1996) Crystal structure of three consecutive laminin-type epidermal growth factor-like (LE) modules of laminin gamma1 chain harboring the nidogen binding site. J Mol Biol 257(3):644–657. doi: 10.1006/jmbi.1996.0191 PubMedCrossRefGoogle Scholar
  22. 22.
    Timpl R, Brown JC (1996) Supramolecular assembly of basement membranes. BioEssays 18(2):123–132. doi: 10.1002/bies.950180208 PubMedCrossRefGoogle Scholar
  23. 23.
    Mayer U, Kohfeldt E, Timpl R (1998) Structural and genetic analysis of laminin-nidogen interaction. Ann N Y Acad Sci 857:130–142PubMedCrossRefGoogle Scholar
  24. 24.
    Yurchenco PD, Patton BL (2009) Developmental and pathogenic mechanisms of basement membrane assembly. Curr Pharm Des 15(12):1277–1294PubMedPubMedCentralCrossRefGoogle Scholar
  25. 25.
    Ekblom P, Ekblom M, Fecker L, Klein G, Zhang HY, Kadoya Y, Chu ML, Mayer U, Timpl R (1994) Role of mesenchymal nidogen for epithelial morphogenesis in vitro. Development 120(7):2003–2014PubMedGoogle Scholar
  26. 26.
    Kadoya Y, Salmivirta K, Talts JF, Kadoya K, Mayer U, Timpl R, Ekblom P (1997) Importance of nidogen binding to laminin gamma1 for branching epithelial morphogenesis of the submandibular gland. Development 124(3):683–691PubMedGoogle Scholar
  27. 27.
    Tunggal J, Wartenberg M, Paulsson M, Smyth N (2003) Expression of the nidogen-binding site of the laminin gamma1 chain disturbs basement membrane formation and maintenance in F9 embryoid bodies. J Cell Sci 116(Pt 5):803–812PubMedCrossRefGoogle Scholar
  28. 28.
    Breitkreutz D, Mirancea N, Schmidt C, Beck R, Werner U, Stark HJ, Gerl M, Fusenig NE (2004) Inhibition of basement membrane formation by a nidogen-binding laminin gamma1-chain fragment in human skin-organotypic cocultures. J Cell Sci 117(Pt 12):2611–2622. doi: 10.1242/jcs.01127 PubMedCrossRefGoogle Scholar
  29. 29.
    Willem M, Miosge N, Halfter W, Smyth N, Jannetti I, Burghart E, Timpl R, Mayer U (2002) Specific ablation of the nidogen-binding site in the laminin gamma1 chain interferes with kidney and lung development. Development 129(11):2711–2722PubMedGoogle Scholar
  30. 30.
    Mokkapati S, Fleger-Weckmann A, Bechtel M, Koch M, Breitkreutz D, Mayer U, Smyth N, Nischt R (2011) Basement membrane deposition of nidogen 1 but not nidogen 2 requires the nidogen binding module of the laminin gamma1 chain. J Biol Chem 286(3):1911–1918. doi: 10.1074/jbc.M110.149864 PubMedCrossRefGoogle Scholar
  31. 31.
    Yue B (2014) Biology of the extracellular matrix: an overview. J Glaucoma 23(8 Suppl 1):S20–S23. doi: 10.1097/IJG.0000000000000108 PubMedCrossRefGoogle Scholar
  32. 32.
    Lu P, Takai K, Weaver VM, Werb Z (2011) Extracellular matrix degradation and remodeling in development and disease. Cold Spring Harb Perspect Biol. doi: 10.1101/cshperspect.a005058 PubMedPubMedCentralGoogle Scholar
  33. 33.
    Yurchenco PD, Smirnov S, Mathus T (2002) Analysis of basement membrane self-assembly and cellular interactions with native and recombinant glycoproteins. Methods Cell Biol 69:111–144PubMedCrossRefGoogle Scholar
  34. 34.
    Colognato H, Yurchenco PD (2000) Form and function: the laminin family of heterotrimers. Dev Dyn 218(2):213–234. doi: 10.1002/(SICI)1097-0177(200006)218:2<213:AID-DVDY1>3.0.CO;2-R PubMedCrossRefGoogle Scholar
  35. 35.
    Hallmann R, Horn N, Selg M, Wendler O, Pausch F, Sorokin LM (2005) Expression and function of laminins in the embryonic and mature vasculature. Physiol Rev 85(3):979–1000. doi: 10.1152/physrev.00014.2004 PubMedCrossRefGoogle Scholar
  36. 36.
    Ekblom P, Lonai P, Talts JF (2003) Expression and biological role of laminin-1. Matrix Biol 22(1):35–47PubMedCrossRefGoogle Scholar
  37. 37.
    Miner JH, Cunningham J, Sanes JR (1998) Roles for laminin in embryogenesis: exencephaly, syndactyly, and placentopathy in mice lacking the laminin alpha5 chain. J Cell Biol 143(6):1713–1723PubMedPubMedCentralCrossRefGoogle Scholar
  38. 38.
    Sasaki T, Fassler R, Hohenester E (2004) Laminin: the crux of basement membrane assembly. J Cell Biol 164(7):959–963. doi: 10.1083/jcb.200401058 PubMedPubMedCentralCrossRefGoogle Scholar
  39. 39.
    Miner JH (2008) Laminins and their roles in mammals. Microsc Res Tech 71(5):349–356. doi: 10.1002/jemt.20563 PubMedCrossRefGoogle Scholar
  40. 40.
    Samuel MA, Valdez G, Tapia JC, Lichtman JW, Sanes JR (2012) Agrin and synaptic laminin are required to maintain adult neuromuscular junctions. PLoS ONE 7(10):e46663. doi: 10.1371/journal.pone.0046663 PubMedPubMedCentralCrossRefGoogle Scholar
  41. 41.
    Patton BL (2000) Laminins of the neuromuscular system. Microsc Res Tech 51(3):247–261. doi: 10.1002/1097-0029(20001101)51:3<247:AID-JEMT5>3.0.CO;2-Z PubMedCrossRefGoogle Scholar
  42. 42.
    Miner JH, Li C, Mudd JL, Go G, Sutherland AE (2004) Compositional and structural requirements for laminin and basement membranes during mouse embryo implantation and gastrulation. Development 131(10):2247–2256. doi: 10.1242/dev.01112 PubMedCrossRefGoogle Scholar
  43. 43.
    Yin Y, Kikkawa Y, Mudd JL, Skarnes WC, Sanes JR, Miner JH (2003) Expression of laminin chains by central neurons: analysis with gene and protein trapping techniques. Genesis 36(2):114–127. doi: 10.1002/gene.10206 PubMedCrossRefGoogle Scholar
  44. 44.
    Virtanen I, Gullberg D, Rissanen J, Kivilaakso E, Kiviluoto T, Laitinen LA, Lehto VP, Ekblom P (2000) Laminin alpha1-chain shows a restricted distribution in epithelial basement membranes of fetal and adult human tissues. Exp Cell Res 257(2):298–309. doi: 10.1006/excr.2000.4883 PubMedCrossRefGoogle Scholar
  45. 45.
    Lentz SI, Miner JH, Sanes JR, Snider WD (1997) Distribution of the ten known laminin chains in the pathways and targets of developing sensory axons. J Comp Neurol 378(4):547–561PubMedCrossRefGoogle Scholar
  46. 46.
    Thomas T, Dziadek M (1993) Genes coding for basement membrane glycoproteins laminin, nidogen, and collagen IV are differentially expressed in the nervous system and by epithelial, endothelial, and mesenchymal cells of the mouse embryo. Exp Cell Res 208(1):54–67. doi: 10.1006/excr.1993.1222 PubMedCrossRefGoogle Scholar
  47. 47.
    Ekblom M, Klein G, Mugrauer G, Fecker L, Deutzmann R, Timpl R, Ekblom P (1990) Transient and locally restricted expression of laminin A chain mRNA by developing epithelial cells during kidney organogenesis. Cell 60(2):337–346PubMedCrossRefGoogle Scholar
  48. 48.
    Alpy F, Jivkov I, Sorokin L, Klein A, Arnold C, Huss Y, Kedinger M, Simon-Assmann P, Lefebvre O (2005) Generation of a conditionally null allele of the laminin alpha1 gene. Genesis 43(2):59–70. doi: 10.1002/gene.20154 PubMedCrossRefGoogle Scholar
  49. 49.
    Scheele S, Falk M, Franzen A, Ellin F, Ferletta M, Lonai P, Andersson B, Timpl R, Forsberg E, Ekblom P (2005) Laminin alpha1 globular domains 4-5 induce fetal development but are not vital for embryonic basement membrane assembly. Proc Natl Acad Sci USA 102(5):1502–1506. doi: 10.1073/pnas.0405095102 PubMedPubMedCentralCrossRefGoogle Scholar
  50. 50.
    Edwards MM, Mammadova-Bach E, Alpy F, Klein A, Hicks WL, Roux M, Simon-Assmann P, Smith RS, Orend G, Wu J, Peachey NS, Naggert JK, Lefebvre O, Nishina PM (2010) Mutations in Lama1 disrupt retinal vascular development and inner limiting membrane formation. J Biol Chem 285(10):7697–7711. doi: 10.1074/jbc.M109.069575 PubMedPubMedCentralCrossRefGoogle Scholar
  51. 51.
    Edwards MM, McLeod DS, Grebe R, Heng C, Lefebvre O, Lutty GA (2011) Lama1 mutations lead to vitreoretinal blood vessel formation, persistence of fetal vasculature, and epiretinal membrane formation in mice. BMC Dev Biol 11:60. doi: 10.1186/1471-213X-11-60 PubMedPubMedCentralCrossRefGoogle Scholar
  52. 52.
    Ichikawa-Tomikawa N, Ogawa J, Douet V, Xu Z, Kamikubo Y, Sakurai T, Kohsaka S, Chiba H, Hattori N, Yamada Y, Arikawa-Hirasawa E (2012) Laminin alpha1 is essential for mouse cerebellar development. Matrix Biol 31(1):17–28. doi: 10.1016/j.matbio.2011.09.002 PubMedCrossRefGoogle Scholar
  53. 53.
    Zinkevich NS, Bosenko DV, Link BA, Semina EV (2006) laminin alpha 1 gene is essential for normal lens development in zebrafish. BMC Dev Biol 6:13. doi: 10.1186/1471-213X-6-13 PubMedPubMedCentralCrossRefGoogle Scholar
  54. 54.
    Karlstrom RO, Trowe T, Klostermann S, Baier H, Brand M, Crawford AD, Grunewald B, Haffter P, Hoffmann H, Meyer SU, Muller BK, Richter S, van Eeden FJ, Nusslein-Volhard C, Bonhoeffer F (1996) Zebrafish mutations affecting retinotectal axon pathfinding. Development 123:427–438PubMedGoogle Scholar
  55. 55.
    Paulus JD, Halloran MC (2006) Zebrafish bashful/laminin-alpha 1 mutants exhibit multiple axon guidance defects. Dev Dyn 235(1):213–224. doi: 10.1002/dvdy.20604 PubMedCrossRefGoogle Scholar
  56. 56.
    Biehlmaier O, Makhankov Y, Neuhauss SC (2007) Impaired retinal differentiation and maintenance in zebrafish laminin mutants. Invest Ophthalmol Vis Sci 48(6):2887–2894. doi: 10.1167/iovs.06-1212 PubMedCrossRefGoogle Scholar
  57. 57.
    Semina EV, Bosenko DV, Zinkevich NC, Soules KA, Hyde DR, Vihtelic TS, Willer GB, Gregg RG, Link BA (2006) Mutations in laminin alpha 1 result in complex, lens-independent ocular phenotypes in zebrafish. Dev Biol 299(1):63–77. doi: 10.1016/j.ydbio.2006.07.005 PubMedCrossRefGoogle Scholar
  58. 58.
    Pathania M, Semina EV, Duncan MK (2014) Lens extrusion from Laminin alpha 1 mutant zebrafish. Sci World J 2014:524929. doi: 10.1155/2014/524929 CrossRefGoogle Scholar
  59. 59.
    Xu H, Christmas P, Wu XR, Wewer UM, Engvall E (1994) Defective muscle basement membrane and lack of M-laminin in the dystrophic dy/dy mouse. Proc Natl Acad Sci USA 91(12):5572–5576PubMedPubMedCentralCrossRefGoogle Scholar
  60. 60.
    Xu H, Wu XR, Wewer UM, Engvall E (1994) Murine muscular dystrophy caused by a mutation in the laminin alpha 2 (Lama2) gene. Nat Genet 8(3):297–302. doi: 10.1038/ng1194-297 PubMedCrossRefGoogle Scholar
  61. 61.
    Tome FM, Evangelista T, Leclerc A, Sunada Y, Manole E, Estournet B, Barois A, Campbell KP, Fardeau M (1994) Congenital muscular dystrophy with merosin deficiency. C R Acad Sci 317(4):351–357Google Scholar
  62. 62.
    Michelson AM, Russell ES, Harman PJ (1955) Dystrophia muscularis: a hereditary primary myopathy in the house mouse. Proc Natl Acad Sci USA 41(12):1079–1084PubMedPubMedCentralCrossRefGoogle Scholar
  63. 63.
    Sunada Y, Bernier SM, Kozak CA, Yamada Y, Campbell KP (1994) Deficiency of merosin in dystrophic dy mice and genetic linkage of laminin M chain gene to dy locus. J Biol Chem 269(19):13729–13732PubMedGoogle Scholar
  64. 64.
    Kuang W, Xu H, Vachon PH, Liu L, Loechel F, Wewer UM, Engvall E (1998) Merosin-deficient congenital muscular dystrophy. Partial genetic correction in two mouse models. J Clin Invest 102(4):844–852. doi: 10.1172/JCI3705 PubMedPubMedCentralCrossRefGoogle Scholar
  65. 65.
    Miyagoe Y, Hanaoka K, Nonaka I, Hayasaka M, Nabeshima Y, Arahata K, Nabeshima Y, Takeda S (1997) Laminin alpha2 chain-null mutant mice by targeted disruption of the Lama2 gene: a new model of merosin (laminin 2)-deficient congenital muscular dystrophy. FEBS Lett 415(1):33–39PubMedCrossRefGoogle Scholar
  66. 66.
    Nakagawa M, Miyagoe-Suzuki Y, Ikezoe K, Miyata Y, Nonaka I, Harii K, Takeda S (2001) Schwann cell myelination occurred without basal lamina formation in laminin alpha2 chain-null mutant (dy3K/dy3K) mice. Glia 35(2):101–110PubMedCrossRefGoogle Scholar
  67. 67.
    Menezes MJ, McClenahan FK, Leiton CV, Aranmolate A, Shan X, Colognato H (2014) The extracellular matrix protein laminin alpha2 regulates the maturation and function of the blood–brain barrier. J Neurosci 34(46):15260–15280. doi: 10.1523/JNEUROSCI.3678-13.2014 PubMedCrossRefGoogle Scholar
  68. 68.
    Sunada Y, Edgar TS, Lotz BP, Rust RS, Campbell KP (1995) Merosin-negative congenital muscular dystrophy associated with extensive brain abnormalities. Neurology 45(11):2084–2089PubMedCrossRefGoogle Scholar
  69. 69.
    Gawlik K, Miyagoe-Suzuki Y, Ekblom P, Takeda S, Durbeej M (2004) Laminin alpha1 chain reduces muscular dystrophy in laminin alpha2 chain deficient mice. Hum Mol Genet 13(16):1775–1784. doi: 10.1093/hmg/ddh190 PubMedCrossRefGoogle Scholar
  70. 70.
    Hager M, Gawlik K, Nystrom A, Sasaki T, Durbeej M (2005) Laminin {alpha}1 chain corrects male infertility caused by absence of laminin {alpha}2 chain. Am J Pathol 167(3):823–833PubMedPubMedCentralCrossRefGoogle Scholar
  71. 71.
    Gawlik KI, Mayer U, Blomberg K, Sonnenberg A, Ekblom P, Durbeej M (2006) Laminin alpha1 chain mediated reduction of laminin alpha2 chain deficient muscular dystrophy involves integrin alpha7beta1 and dystroglycan. FEBS Lett 580(7):1759–1765. doi: 10.1016/j.febslet.2006.02.027 PubMedCrossRefGoogle Scholar
  72. 72.
    Gawlik KI, Durbeej M (2010) Transgenic overexpression of laminin alpha1 chain in laminin alpha2 chain-deficient mice rescues the disease throughout the lifespan. Muscle Nerve 42(1):30–37. doi: 10.1002/mus.21616 PubMedCrossRefGoogle Scholar
  73. 73.
    Gawlik KI, Li JY, Petersen A, Durbeej M (2006) Laminin alpha1 chain improves laminin alpha2 chain deficient peripheral neuropathy. Hum Mol Genet 15(18):2690–2700. doi: 10.1093/hmg/ddl201 PubMedCrossRefGoogle Scholar
  74. 74.
    Gawlik KI, Akerlund M, Carmignac V, Elamaa H, Durbeej M (2010) Distinct roles for laminin globular domains in laminin alpha1 chain mediated rescue of murine laminin alpha2 chain deficiency. PLoS ONE 5(7):e11549. doi: 10.1371/journal.pone.0011549 PubMedPubMedCentralCrossRefGoogle Scholar
  75. 75.
    Rooney JE, Knapp JR, Hodges BL, Wuebbles RD, Burkin DJ (2012) Laminin-111 protein therapy reduces muscle pathology and improves viability of a mouse model of merosin-deficient congenital muscular dystrophy. Am J Pathol 180(4):1593–1602. doi: 10.1016/j.ajpath.2011.12.019 PubMedPubMedCentralCrossRefGoogle Scholar
  76. 76.
    Van Ry PM, Minogue P, Hodges BL, Burkin DJ (2014) Laminin-111 improves muscle repair in a mouse model of merosin-deficient congenital muscular dystrophy. Hum Mol Genet 23(2):383–396. doi: 10.1093/hmg/ddt428 PubMedCrossRefGoogle Scholar
  77. 77.
    Goudenege S, Lamarre Y, Dumont N, Rousseau J, Frenette J, Skuk D, Tremblay JP (2010) Laminin-111: a potential therapeutic agent for Duchenne muscular dystrophy. Mol Therapy 18(12):2155–2163. doi: 10.1038/mt.2010.165 CrossRefGoogle Scholar
  78. 78.
    Rooney JE, Gurpur PB, Burkin DJ (2009) Laminin-111 protein therapy prevents muscle disease in the mdx mouse model for Duchenne muscular dystrophy. Proc Natl Acad Sci USA 106(19):7991–7996. doi: 10.1073/pnas.0811599106 PubMedPubMedCentralCrossRefGoogle Scholar
  79. 79.
    Yao Y, Norris EH, Widdowson EM, Strickland S (2016) Laminin regulates PDGFRbeta cell stemness and muscle development. Nat Commun 7:11415. doi: 10.1038/ncomms11415 PubMedPubMedCentralCrossRefGoogle Scholar
  80. 80.
    Moll J, Barzaghi P, Lin S, Bezakova G, Lochmuller H, Engvall E, Muller U, Ruegg MA (2001) An agrin minigene rescues dystrophic symptoms in a mouse model for congenital muscular dystrophy. Nature 413(6853):302–307. doi: 10.1038/35095054 PubMedCrossRefGoogle Scholar
  81. 81.
    Bentzinger CF, Barzaghi P, Lin S, Ruegg MA (2005) Overexpression of mini-agrin in skeletal muscle increases muscle integrity and regenerative capacity in laminin-alpha2-deficient mice. FASEB J 19(8):934–942. doi: 10.1096/fj.04-3376com PubMedCrossRefGoogle Scholar
  82. 82.
    Meinen S, Barzaghi P, Lin S, Lochmuller H, Ruegg MA (2007) Linker molecules between laminins and dystroglycan ameliorate laminin-alpha2-deficient muscular dystrophy at all disease stages. J Cell Biol 176(7):979–993. doi: 10.1083/jcb.200611152 PubMedPubMedCentralCrossRefGoogle Scholar
  83. 83.
    Qiao C, Li J, Zhu T, Draviam R, Watkins S, Ye X, Chen C, Li J, Xiao X (2005) Amelioration of laminin-alpha2-deficient congenital muscular dystrophy by somatic gene transfer of miniagrin. Proc Natl Acad Sci USA 102(34):11999–12004. doi: 10.1073/pnas.0502137102 PubMedPubMedCentralCrossRefGoogle Scholar
  84. 84.
    Girgenrath M, Dominov JA, Kostek CA, Miller JB (2004) Inhibition of apoptosis improves outcome in a model of congenital muscular dystrophy. J Clin Investig 114(11):1635–1639. doi: 10.1172/JCI22928 PubMedPubMedCentralCrossRefGoogle Scholar
  85. 85.
    Girgenrath M, Beermann ML, Vishnudas VK, Homma S, Miller JB (2009) Pathology is alleviated by doxycycline in a laminin-alpha2-null model of congenital muscular dystrophy. Ann Neurol 65(1):47–56. doi: 10.1002/ana.21523 PubMedPubMedCentralCrossRefGoogle Scholar
  86. 86.
    Erb M, Meinen S, Barzaghi P, Sumanovski LT, Courdier-Fruh I, Ruegg MA, Meier T (2009) Omigapil ameliorates the pathology of muscle dystrophy caused by laminin-alpha2 deficiency. J Pharmacol Exp Ther 331(3):787–795. doi: 10.1124/jpet.109.160754 PubMedCrossRefGoogle Scholar
  87. 87.
    Carmignac V, Quere R, Durbeej M (2011) Proteasome inhibition improves the muscle of laminin alpha2 chain-deficient mice. Hum Mol Genet 20(3):541–552. doi: 10.1093/hmg/ddq499 PubMedCrossRefGoogle Scholar
  88. 88.
    Korner Z, Fontes-Oliveira CC, Holmberg J, Carmignac V, Durbeej M (2014) Bortezomib partially improves laminin alpha2 chain-deficient muscular dystrophy. Am J Pathol 184(5):1518–1528. doi: 10.1016/j.ajpath.2014.01.019 PubMedCrossRefGoogle Scholar
  89. 89.
    Carmignac V, Svensson M, Korner Z, Elowsson L, Matsumura C, Gawlik KI, Allamand V, Durbeej M (2011) Autophagy is increased in laminin alpha2 chain-deficient muscle and its inhibition improves muscle morphology in a mouse model of MDC1A. Hum Mol Genet 20(24):4891–4902. doi: 10.1093/hmg/ddr427 PubMedCrossRefGoogle Scholar
  90. 90.
    Meinen S, Lin S, Ruegg MA (2012) Angiotensin II type 1 receptor antagonists alleviate muscle pathology in the mouse model for laminin-alpha2-deficient congenital muscular dystrophy (MDC1A). Skelet Muscle 2(1):18. doi: 10.1186/2044-5040-2-18 PubMedPubMedCentralCrossRefGoogle Scholar
  91. 91.
    Meinen S, Lin S, Thurnherr R, Erb M, Meier T, Ruegg MA (2011) Apoptosis inhibitors and mini-agrin have additive benefits in congenital muscular dystrophy mice. EMBO Mol Med 3(8):465–479. doi: 10.1002/emmm.201100151 PubMedPubMedCentralCrossRefGoogle Scholar
  92. 92.
    Yamauchi J, Kumar A, Duarte L, Mehuron T, Girgenrath M (2013) Triggering regeneration and tackling apoptosis: a combinatorial approach to treating congenital muscular dystrophy type 1 A. Hum Mol Genet 22(21):4306–4317. doi: 10.1093/hmg/ddt280 PubMedCrossRefGoogle Scholar
  93. 93.
    Durbeej M (2015) Laminin-alpha2 chain-deficient congenital muscular dystrophy: pathophysiology and development of treatment. Curr Top Membr 76:31–60. doi: 10.1016/bs.ctm.2015.05.002 PubMedCrossRefGoogle Scholar
  94. 94.
    Carter WG, Ryan MC, Gahr PJ (1991) Epiligrin, a new cell adhesion ligand for integrin alpha 3 beta 1 in epithelial basement membranes. Cell 65(4):599–610PubMedCrossRefGoogle Scholar
  95. 95.
    Aberdam D, Galliano MF, Vailly J, Pulkkinen L, Bonifas J, Christiano AM, Tryggvason K, Uitto J, Epstein EH Jr, Ortonne JP et al (1994) Herlitz’s junctional epidermolysis bullosa is linked to mutations in the gene (LAMC2) for the gamma 2 subunit of nicein/kalinin (LAMININ-5). Nat Genet 6(3):299–304. doi: 10.1038/ng0394-299 PubMedCrossRefGoogle Scholar
  96. 96.
    Ryan MC, Lee K, Miyashita Y, Carter WG (1999) Targeted disruption of the LAMA3 gene in mice reveals abnormalities in survival and late stage differentiation of epithelial cells. J Cell Biol 145(6):1309–1323PubMedPubMedCentralCrossRefGoogle Scholar
  97. 97.
    McGrath JA, Kivirikko S, Ciatti S, Moss C, Dunnill GS, Eady RA, Rodeck CH, Christiano AM, Uitto J (1995) A homozygous nonsense mutation in the alpha 3 chain gene of laminin 5 (LAMA3) in Herlitz junctional epidermolysis bullosa: prenatal exclusion in a fetus at risk. Genomics 29(1):282–284PubMedCrossRefGoogle Scholar
  98. 98.
    Urich D, Eisenberg JL, Hamill KJ, Takawira D, Chiarella SE, Soberanes S, Gonzalez A, Koentgen F, Manghi T, Hopkinson SB, Misharin AV, Perlman H, Mutlu GM, Budinger GR, Jones JC (2011) Lung-specific loss of the laminin alpha3 subunit confers resistance to mechanical injury. J Cell Sci 124(Pt 17):2927–2937. doi: 10.1242/jcs.080911 PubMedPubMedCentralCrossRefGoogle Scholar
  99. 99.
    Frieser M, Nockel H, Pausch F, Roder C, Hahn A, Deutzmann R, Sorokin LM (1997) Cloning of the mouse laminin alpha 4 cDNA. Expression in a subset of endothelium. Eur J Biochem/FEBS 246 (3):727–735Google Scholar
  100. 100.
    Iivanainen A, Kortesmaa J, Sahlberg C, Morita T, Bergmann U, Thesleff I, Tryggvason K (1997) Primary structure, developmental expression, and immunolocalization of the murine laminin alpha4 chain. J Biol Chem 272(44):27862–27868PubMedCrossRefGoogle Scholar
  101. 101.
    Lefebvre O, Sorokin L, Kedinger M, Simon-Assmann P (1999) Developmental expression and cellular origin of the laminin alpha2, alpha4, and alpha5 chains in the intestine. Dev Biol 210(1):135–150. doi: 10.1006/dbio.1999.9270 PubMedCrossRefGoogle Scholar
  102. 102.
    Patton BL, Miner JH, Chiu AY, Sanes JR (1997) Distribution and function of laminins in the neuromuscular system of developing, adult, and mutant mice. J Cell Biol 139(6):1507–1521PubMedPubMedCentralCrossRefGoogle Scholar
  103. 103.
    Thyboll J, Kortesmaa J, Cao R, Soininen R, Wang L, Iivanainen A, Sorokin L, Risling M, Cao Y, Tryggvason K (2002) Deletion of the laminin alpha4 chain leads to impaired microvessel maturation. Mol Cell Biol 22(4):1194–1202PubMedPubMedCentralCrossRefGoogle Scholar
  104. 104.
    Wu C, Ivars F, Anderson P, Hallmann R, Vestweber D, Nilsson P, Robenek H, Tryggvason K, Song J, Korpos E, Loser K, Beissert S, Georges-Labouesse E, Sorokin LM (2009) Endothelial basement membrane laminin alpha5 selectively inhibits T lymphocyte extravasation into the brain. Nat Med 15(5):519–527. doi: 10.1038/nm.1957 PubMedCrossRefGoogle Scholar
  105. 105.
    Patton BL, Cunningham JM, Thyboll J, Kortesmaa J, Westerblad H, Edstrom L, Tryggvason K, Sanes JR (2001) Properly formed but improperly localized synaptic specializations in the absence of laminin alpha4. Nat Neurosci 4(6):597–604. doi: 10.1038/88414 PubMedCrossRefGoogle Scholar
  106. 106.
    Abrass CK, Hansen KM, Patton BL (2010) Laminin alpha4-null mutant mice develop chronic kidney disease with persistent overexpression of platelet-derived growth factor. Am J Pathol 176(2):839–849. doi: 10.2353/ajpath.2010.090570 PubMedPubMedCentralCrossRefGoogle Scholar
  107. 107.
    Vaicik MK, Thyboll Kortesmaa J, Moverare-Skrtic S, Kortesmaa J, Soininen R, Bergstrom G, Ohlsson C, Chong LY, Rozell B, Emont M, Cohen RN, Brey EM, Tryggvason K (2014) Laminin alpha4 deficient mice exhibit decreased capacity for adipose tissue expansion and weight gain. PLoS ONE 9(10):e109854. doi: 10.1371/journal.pone.0109854 PubMedPubMedCentralCrossRefGoogle Scholar
  108. 108.
    Yang D, Bierman J, Tarumi YS, Zhong YP, Rangwala R, Proctor TM, Miyagoe-Suzuki Y, Takeda S, Miner JH, Sherman LS, Gold BG, Patton BL (2005) Coordinate control of axon defasciculation and myelination by laminin-2 and -8. J Cell Biol 168(4):655–666. doi: 10.1083/jcb.200411158 PubMedPubMedCentralCrossRefGoogle Scholar
  109. 109.
    Miner JH, Li C, Patton BL (2004) Laminins alpha2 and alpha4 in pancreatic acinar basement membranes are required for basal receptor localization. J Histochem Cytochem 52(2):153–156PubMedCrossRefGoogle Scholar
  110. 110.
    Coles EG, Gammill LS, Miner JH, Bronner-Fraser M (2006) Abnormalities in neural crest cell migration in laminin alpha5 mutant mice. Dev Biol 289(1):218–228. doi: 10.1016/j.ydbio.2005.10.031 PubMedCrossRefGoogle Scholar
  111. 111.
    Miner JH, Li C (2000) Defective glomerulogenesis in the absence of laminin alpha5 demonstrates a developmental role for the kidney glomerular basement membrane. Dev Biol 217(2):278–289. doi: 10.1006/dbio.1999.9546 PubMedCrossRefGoogle Scholar
  112. 112.
    Nguyen NM, Miner JH, Pierce RA, Senior RM (2002) Laminin alpha 5 is required for lobar septation and visceral pleural basement membrane formation in the developing mouse lung. Dev Biol 246(2):231–244. doi: 10.1006/dbio.2002.0658 PubMedCrossRefGoogle Scholar
  113. 113.
    Gao J, DeRouen MC, Chen CH, Nguyen M, Nguyen NT, Ido H, Harada K, Sekiguchi K, Morgan BA, Miner JH, Oro AE, Marinkovich MP (2008) Laminin-511 is an epithelial message promoting dermal papilla development and function during early hair morphogenesis. Genes Dev 22(15):2111–2124. doi: 10.1101/gad.1689908 PubMedPubMedCentralCrossRefGoogle Scholar
  114. 114.
    Li J, Tzu J, Chen Y, Zhang YP, Nguyen NT, Gao J, Bradley M, Keene DR, Oro AE, Miner JH, Marinkovich MP (2003) Laminin-10 is crucial for hair morphogenesis. EMBO J 22(10):2400–2410. doi: 10.1093/emboj/cdg239 PubMedPubMedCentralCrossRefGoogle Scholar
  115. 115.
    Mahoney ZX, Stappenbeck TS, Miner JH (2008) Laminin alpha 5 influences the architecture of the mouse small intestine mucosa. J Cell Sci 121(Pt 15):2493–2502. doi: 10.1242/jcs.025528 PubMedPubMedCentralCrossRefGoogle Scholar
  116. 116.
    Ritie L, Spenle C, Lacroute J, Bolcato-Bellemin AL, Lefebvre O, Bole-Feysot C, Jost B, Klein A, Arnold C, Kedinger M, Bagnard D, Orend G, Simon-Assmann P (2012) Abnormal Wnt and PI3Kinase signaling in the malformed intestine of lama5 deficient mice. PLoS ONE 7(5):e37710. doi: 10.1371/journal.pone.0037710 PubMedPubMedCentralCrossRefGoogle Scholar
  117. 117.
    Bolcato-Bellemin AL, Lefebvre O, Arnold C, Sorokin L, Miner JH, Kedinger M, Simon-Assmann P (2003) Laminin alpha5 chain is required for intestinal smooth muscle development. Dev Biol 260(2):376–390PubMedCrossRefGoogle Scholar
  118. 118.
    Kikkawa Y, Miner JH (2006) Molecular dissection of laminin alpha 5 in vivo reveals separable domain-specific roles in embryonic development and kidney function. Dev Biol 296(1):265–277. doi: 10.1016/j.ydbio.2006.04.463 PubMedCrossRefGoogle Scholar
  119. 119.
    Nishimune H, Valdez G, Jarad G, Moulson CL, Muller U, Miner JH, Sanes JR (2008) Laminins promote postsynaptic maturation by an autocrine mechanism at the neuromuscular junction. J Cell Biol 182(6):1201–1215. doi: 10.1083/jcb.200805095 PubMedPubMedCentralCrossRefGoogle Scholar
  120. 120.
    Shannon MB, Patton BL, Harvey SJ, Miner JH (2006) A hypomorphic mutation in the mouse laminin alpha5 gene causes polycystic kidney disease. J Am Soc Nephrol JASN 17(7):1913–1922. doi: 10.1681/ASN.2005121298 PubMedCrossRefGoogle Scholar
  121. 121.
    Goldberg S, Adair-Kirk TL, Senior RM, Miner JH (2010) Maintenance of glomerular filtration barrier integrity requires laminin alpha5. J Am Soc Nephrol JASN 21(4):579–586. doi: 10.1681/ASN.2009091004 PubMedCrossRefGoogle Scholar
  122. 122.
    Fukumoto S, Miner JH, Ida H, Fukumoto E, Yuasa K, Miyazaki H, Hoffman MP, Yamada Y (2006) Laminin alpha5 is required for dental epithelium growth and polarity and the development of tooth bud and shape. J Biol Chem 281(8):5008–5016. doi: 10.1074/jbc.M509295200 PubMedCrossRefGoogle Scholar
  123. 123.
    Rebustini IT, Patel VN, Stewart JS, Layvey A, Georges-Labouesse E, Miner JH, Hoffman MP (2007) Laminin alpha5 is necessary for submandibular gland epithelial morphogenesis and influences FGFR expression through beta1 integrin signaling. Dev Biol 308(1):15–29. doi: 10.1016/j.ydbio.2007.04.031 PubMedPubMedCentralCrossRefGoogle Scholar
  124. 124.
    Nguyen NM, Kelley DG, Schlueter JA, Meyer MJ, Senior RM, Miner JH (2005) Epithelial laminin alpha5 is necessary for distal epithelial cell maturation, VEGF production, and alveolization in the developing murine lung. Dev Biol 282(1):111–125. doi: 10.1016/j.ydbio.2005.02.031 PubMedCrossRefGoogle Scholar
  125. 125.
    Liu YB, Tewari A, Salameh J, Arystarkhova E, Hampton TG, Brashear A, Ozelius LJ, Khodakhah K, Sweadner KJ (2015) A dystonia-like movement disorder with brain and spinal neuronal defects is caused by mutation of the mouse laminin beta1 subunit, Lamb1. eLife 4. doi:10.7554/eLife.11102Google Scholar
  126. 126.
    Noakes PG, Gautam M, Mudd J, Sanes JR, Merlie JP (1995) Aberrant differentiation of neuromuscular junctions in mice lacking s-laminin/laminin beta 2. Nature 374(6519):258–262. doi: 10.1038/374258a0 PubMedCrossRefGoogle Scholar
  127. 127.
    Noakes PG, Miner JH, Gautam M, Cunningham JM, Sanes JR, Merlie JP (1995) The renal glomerulus of mice lacking s-laminin/laminin beta 2: nephrosis despite molecular compensation by laminin beta 1. Nat Genet 10(4):400–406. doi: 10.1038/ng0895-400 PubMedCrossRefGoogle Scholar
  128. 128.
    Miner JH, Go G, Cunningham J, Patton BL, Jarad G (2006) Transgenic isolation of skeletal muscle and kidney defects in laminin beta2 mutant mice: implications for Pierson syndrome. Development 133(5):967–975. doi: 10.1242/dev.02270 PubMedPubMedCentralCrossRefGoogle Scholar
  129. 129.
    Jarad G, Cunningham J, Shaw AS, Miner JH (2006) Proteinuria precedes podocyte abnormalities inLamb2−/− mice, implicating the glomerular basement membrane as an albumin barrier. J Clin Investig 116(8):2272–2279. doi: 10.1172/JCI28414 PubMedPubMedCentralCrossRefGoogle Scholar
  130. 130.
    Libby RT, Lavallee CR, Balkema GW, Brunken WJ, Hunter DD (1999) Disruption of laminin beta2 chain production causes alterations in morphology and function in the CNS. J Neurosci 19(21):9399–9411PubMedGoogle Scholar
  131. 131.
    Denes V, Witkovsky P, Koch M, Hunter DD, Pinzon-Duarte G, Brunken WJ (2007) Laminin deficits induce alterations in the development of dopaminergic neurons in the mouse retina. Vis Neurosci 24(4):549–562. doi: 10.1017/S0952523807070514 PubMedPubMedCentralCrossRefGoogle Scholar
  132. 132.
    Zenker M, Tralau T, Lennert T, Pitz S, Mark K, Madlon H, Dotsch J, Reis A, Muntefering H, Neumann LM (2004) Congenital nephrosis, mesangial sclerosis, and distinct eye abnormalities with microcoria: an autosomal recessive syndrome. Am J Med Genet Part A 130A(2):138–145. doi: 10.1002/ajmg.a.30310 PubMedCrossRefGoogle Scholar
  133. 133.
    Zenker M, Pierson M, Jonveaux P, Reis A (2005) Demonstration of two novel LAMB2 mutations in the original Pierson syndrome family reported 42 years ago. Am J Med Genet Part A 138(1):73–74. doi: 10.1002/ajmg.a.30894 PubMedCrossRefGoogle Scholar
  134. 134.
    Zenker M, Aigner T, Wendler O, Tralau T, Muntefering H, Fenski R, Pitz S, Schumacher V, Royer-Pokora B, Wuhl E, Cochat P, Bouvier R, Kraus C, Mark K, Madlon H, Dotsch J, Rascher W, Maruniak-Chudek I, Lennert T, Neumann LM, Reis A (2004) Human laminin beta2 deficiency causes congenital nephrosis with mesangial sclerosis and distinct eye abnormalities. Hum Mol Genet 13(21):2625–2632. doi: 10.1093/hmg/ddh284 PubMedCrossRefGoogle Scholar
  135. 135.
    Kuster JE, Guarnieri MH, Ault JG, Flaherty L, Swiatek PJ (1997) IAP insertion in the murine LamB3 gene results in junctional epidermolysis bullosa. Mamm Genome 8(9):673–681PubMedCrossRefGoogle Scholar
  136. 136.
    Muhle C, Neuner A, Park J, Pacho F, Jiang Q, Waddington SN, Schneider H (2006) Evaluation of prenatal intra-amniotic LAMB3 gene delivery in a mouse model of Herlitz disease. Gene Ther 13(23):1665–1676. doi: 10.1038/ PubMedCrossRefGoogle Scholar
  137. 137.
    Hammersen J, Hou J, Wunsche S, Brenner S, Winkler T, Schneider H (2015) A new mouse model of junctional epidermolysis bullosa: the LAMB3 628G>A knockin mouse. J Invest Dermatol 135(3):921–924. doi: 10.1038/jid.2014.466 PubMedCrossRefGoogle Scholar
  138. 138.
    Smith CG, Naven M, Harris R, Colley J, West H, Li N, Liu Y, Adams R, Maughan TS, Nichols L, Kaplan R, Wagner MJ, McLeod HL, Cheadle JP (2013) Exome resequencing identifies potential tumor-suppressor genes that predispose to colorectal cancer. Hum Mutat 34(7):1026–1034. doi: 10.1002/humu.22333 PubMedCrossRefGoogle Scholar
  139. 139.
    Choi MR, An CH, Yoo NJ, Lee SH (2015) Laminin gene LAMB4 is somatically mutated and expressionally altered in gastric and colorectal cancers. APMIS 123(1):65–71. doi: 10.1111/apm.12309 PubMedCrossRefGoogle Scholar
  140. 140.
    Miner JH, Patton BL, Lentz SI, Gilbert DJ, Snider WD, Jenkins NA, Copeland NG, Sanes JR (1997) The laminin alpha chains: expression, developmental transitions, and chromosomal locations of alpha1-5, identification of heterotrimeric laminins 8–11, and cloning of a novel alpha3 isoform. J Cell Biol 137(3):685–701PubMedPubMedCentralCrossRefGoogle Scholar
  141. 141.
    Smyth N, Vatansever HS, Meyer M, Frie C, Paulsson M, Edgar D (1998) The targeted deletion of the LAMC1 gene. Ann N Y Acad Sci 857:283–286PubMedCrossRefGoogle Scholar
  142. 142.
    Smyth N, Vatansever HS, Murray P, Meyer M, Frie C, Paulsson M, Edgar D (1999) Absence of basement membranes after targeting the LAMC1 gene results in embryonic lethality due to failure of endoderm differentiation. J Cell Biol 144(1):151–160PubMedPubMedCentralCrossRefGoogle Scholar
  143. 143.
    Murray P, Edgar D (2000) Regulation of programmed cell death by basement membranes in embryonic development. J Cell Biol 150(5):1215–1221PubMedPubMedCentralCrossRefGoogle Scholar
  144. 144.
    Chen ZL, Strickland S (2003) Laminin gamma1 is critical for Schwann cell differentiation, axon myelination, and regeneration in the peripheral nerve. J Cell Biol 163(4):889–899. doi: 10.1083/jcb.200307068 PubMedPubMedCentralCrossRefGoogle Scholar
  145. 145.
    Chen ZL, Haegeli V, Yu H, Strickland S (2009) Cortical deficiency of laminin gamma1 impairs the AKT/GSK-3beta signaling pathway and leads to defects in neurite outgrowth and neuronal migration. Dev Biol 327(1):158–168. doi: 10.1016/j.ydbio.2008.12.006 PubMedCrossRefGoogle Scholar
  146. 146.
    Yu WM, Feltri ML, Wrabetz L, Strickland S, Chen ZL (2005) Schwann cell-specific ablation of laminin gamma1 causes apoptosis and prevents proliferation. J Neurosci 25(18):4463–4472. doi: 10.1523/JNEUROSCI.5032-04.2005 PubMedPubMedCentralCrossRefGoogle Scholar
  147. 147.
    Yang DH, McKee KK, Chen ZL, Mernaugh G, Strickland S, Zent R, Yurchenco PD (2011) Renal collecting system growth and function depend upon embryonic gamma1 laminin expression. Development 138(20):4535–4544. doi: 10.1242/dev.071266 PubMedPubMedCentralCrossRefGoogle Scholar
  148. 148.
    Chen ZL, Yao Y, Norris EH, Kruyer A, Jno-Charles O, Akhmerov A, Strickland S (2013) Ablation of astrocytic laminin impairs vascular smooth muscle cell function and leads to hemorrhagic stroke. J Cell Biol 202(2):381–395. doi: 10.1083/jcb.201212032 PubMedPubMedCentralCrossRefGoogle Scholar
  149. 149.
    Yao Y, Chen ZL, Norris EH, Strickland S (2014) Astrocytic laminin regulates pericyte differentiation and maintains blood brain barrier integrity. Nat Commun 5:3413. doi: 10.1038/ncomms4413 PubMedPubMedCentralGoogle Scholar
  150. 150.
    Yao Y, Norris EH, Strickland S (2015) The cellular origin of laminin determines its role in blood pressure regulation. Cell Mol Life Sci 72(5):999–1008. doi: 10.1007/s00018-014-1732-y PubMedCrossRefGoogle Scholar
  151. 151.
    Pulkkinen L, Christiano AM, Airenne T, Haakana H, Tryggvason K, Uitto J (1994) Mutations in the gamma 2 chain gene (LAMC2) of kalinin/laminin 5 in the junctional forms of epidermolysis bullosa. Nat Genet 6(3):293–297. doi: 10.1038/ng0394-293 PubMedCrossRefGoogle Scholar
  152. 152.
    Meng X, Klement JF, Leperi DA, Birk DE, Sasaki T, Timpl R, Uitto J, Pulkkinen L (2003) Targeted inactivation of murine laminin gamma2-chain gene recapitulates human junctional epidermolysis bullosa. J Invest Dermatol 121(4):720–731. doi: 10.1046/j.1523-1747.2003.12515.x PubMedCrossRefGoogle Scholar
  153. 153.
    Nguyen NM, Pulkkinen L, Schlueter JA, Meneguzzi G, Uitto J, Senior RM (2006) Lung development in laminin gamma2 deficiency: abnormal tracheal hemidesmosomes with normal branching morphogenesis and epithelial differentiation. Respir Res 7:28. doi: 10.1186/1465-9921-7-28 PubMedPubMedCentralCrossRefGoogle Scholar
  154. 154.
    Adair-Kirk TL, Griffin GL, Meyer MJ, Kelley DG, Miner JH, Keene DR, Marinkovich MP, Ruppert JM, Uitto J, Senior RM (2012) Keratinocyte-targeted expression of human laminin gamma2 rescues skin blistering and early lethality of laminin gamma2 deficient mice. PLoS ONE 7(9):e45546. doi: 10.1371/journal.pone.0045546 PubMedPubMedCentralCrossRefGoogle Scholar
  155. 155.
    Li YN, Radner S, French MM, Pinzon-Duarte G, Daly GH, Burgeson RE, Koch M, Brunken WJ (2012) The gamma3 chain of laminin is widely but differentially expressed in murine basement membranes: expression and functional studies. Matrix Biol 31(2):120–134. doi: 10.1016/j.matbio.2011.12.002 PubMedCrossRefGoogle Scholar
  156. 156.
    Radner S, Banos C, Bachay G, Li YN, Hunter DD, Brunken WJ, Yee KT (2013) beta2 and gamma3 laminins are critical cortical basement membrane components: ablation of Lamb2 and Lamc3 genes disrupts cortical lamination and produces dysplasia. Dev Neurobiol 73(3):209–229. doi: 10.1002/dneu.22057 PubMedCrossRefGoogle Scholar
  157. 157.
    Pinzon-Duarte G, Daly G, Li YN, Koch M, Brunken WJ (2010) Defective formation of the inner limiting membrane in laminin beta2- and gamma3-null mice produces retinal dysplasia. Invest Ophthalmol Vis Sci 51(3):1773–1782. doi: 10.1167/iovs.09-4645 PubMedPubMedCentralCrossRefGoogle Scholar
  158. 158.
    Hirrlinger PG, Pannicke T, Winkler U, Claudepierre T, Varshney S, Schulze C, Reichenbach A, Brunken WJ, Hirrlinger J (2011) Genetic deletion of laminin isoforms beta2 and gamma3 induces a reduction in Kir4.1 and aquaporin-4 expression and function in the retina. PLoS ONE 6(1):e16106. doi: 10.1371/journal.pone.0016106 PubMedPubMedCentralCrossRefGoogle Scholar
  159. 159.
    Gnanaguru G, Bachay G, Biswas S, Pinzon-Duarte G, Hunter DD, Brunken WJ (2013) Laminins containing the beta2 and gamma3 chains regulate astrocyte migration and angiogenesis in the retina. Development 140(9):2050–2060. doi: 10.1242/dev.087817 PubMedPubMedCentralCrossRefGoogle Scholar

Copyright information

© Springer International Publishing 2016

Authors and Affiliations

  1. 1.College of PharmacyUniversity of MinnesotaDuluthUSA

Personalised recommendations