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Gene Review

Lama2  -  laminin, alpha 2

Mus musculus

Synonyms: 5830440B04, Laminin M chain, Laminin subunit alpha-2, Laminin-12 subunit alpha, Laminin-2 subunit alpha, ...
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Disease relevance of Lama2

  • Murine muscular dystrophy caused by a mutation in the laminin alpha 2 (Lama2) gene [1].
  • Bax inactivation also improved postnatal growth rate and myofiber histology and decreased fixed contractures of Lama2(-/-) mice [2].
  • Our results indicate that merosin deficiency may be the primary defect in dy mice and suggest that a disruption of the link between alpha-dystroglycan and merosin may be involved in the pathogenesis of muscle degeneration and peripheral neuropathy in dy mice [3].
  • Using a reporter construct, the short-term efficacy of fiber transduction reached 40% and was similar in wild-type, dy/dy and dy(2J)/dy(2J) animals, indicating that ongoing muscle fibrosis was not a major obstacle to the electrotransfer-mediated gene transfer [4].
  • Humans with merosin-deficient congenital muscular dystrophy have both sucking problems during infancy and sleep-disordered breathing during childhood [5].

Psychiatry related information on Lama2

  • The dy/dy mice demonstrated elevated auditory thresholds ranging from 25 to 27 dB at each frequency tested (p<0.0001) [6].

High impact information on Lama2

  • Using recombinant fragments of LN-alpha2 (rLN-alpha2), the M. leprae-binding site was localized to the G domain. rLN-alpha2G mediated M. leprae binding to cell lines and to sciatic nerves of dystrophic dy/dy mice lacking LN-alpha2, but expressing laminin receptors [7].
  • The transgene restores the synthesis and localization of merosin in skeletal muscle, and greatly improves muscle morphology and integrity and the health and longevity of the mice [8].
  • We have expressed a human laminin alpha2 chain transgene under the regulation of a muscle-specific creatine kinase promoter in mice with complete or partial deficiency of merosin [8].
  • Analyses of integrins showed an abnormal expression and localization of alpha7beta1 isoforms in myofibers of merosin-deficient human patients and mice, but not in dystrophin-deficient or sarcoglycan-deficient humans and animals [9].
  • Mutations in genes coding for dystrophin, for alpha, beta, gamma, and delta-sarcoglycans, or for the alpha2 chain of the basement membrane component merosin (laminin-2/4) cause various forms of muscular dystrophy [9].

Chemical compound and disease context of Lama2


Biological context of Lama2


Anatomical context of Lama2


Associations of Lama2 with chemical compounds

  • The binding of laminin and merosin is Ca2+ dependent and is inhibited by NaCl and heparin [20].
  • Binding was inhibited by antibodies recognizing VLA alpha 6 or beta 1, suggesting that the VLA-6 integrin is a merosin receptor [21].
  • Thirty-one mer phosphorothioate oligodeoxynucleotide complementary to the SES of dystrophin exon 19 was intraperitoneally administered to mdx mice without any carrier [22].
  • We find that induction of AChR clustering in C2 myotubes is specific for laminin-1; neither laminin-2 (merosin) nor laminin-11 (a synapse-specific isoform) are active [23].
  • The potassium-channel blocker, 3,4-diaminopyridine, increased force of dy/dy sternohyoid muscle during twitch and 25-Hz contractions by 148 +/- 20% (p < 0.00001) and 109 +/- 18% (p < 0.00002), respectively [5].

Physical interactions of Lama2


Regulatory relationships of Lama2

  • Differential heparin sensitivity of alpha-dystroglycan binding to laminins expressed in normal and dy/dy mouse skeletal muscle [24].
  • In addition to laminin-1, merosin (laminin-2/4) is present both before and after formation of neuromuscular junctions and also promotes AChR clustering and colocalization with the integrin as well as synergism with agrin [25].
  • Overexpression of the apoptosis-suppressing molecule Bcl-2 also promoted the survival of merosin-deficient myotubes, but did not restore a normal expression of alpha7beta1D integrins [9].
  • Relationship between neuronal migration and cell-substratum adhesion: laminin and merosin promote olfactory neuronal migration but are anti-adhesive [26].

Other interactions of Lama2

  • Studies with antisera raised against a DMDL fusion protein identify a 400,000 Mr protein in all mouse tissues tested, including those of mdx and dy mice [16].
  • The interaction between alpha-dystroglycan and merosin may play a role in the regulation of Schwann cell myelination and/or maintenance of myelin sheath [20].
  • Analysis of RNA from the hindlimbs of dy/dy mice demonstrated that in the absence of laminin alpha7 gene transcription is inhibited and limited to specific alternatively spliced isoforms [11].
  • Elimination of myostatin does not combat muscular dystrophy in dy mice but increases postnatal lethality [27].
  • In the present study, we tested the effect of overexpressing ADAM12 in dy(W) laminin-deficient mice. dy mice have a very severe clinical phenotype and would be expected to benefit greatly from enhanced regeneration [28].

Analytical, diagnostic and therapeutic context of Lama2


  1. Murine muscular dystrophy caused by a mutation in the laminin alpha 2 (Lama2) gene. Xu, H., Wu, X.R., Wewer, U.M., Engvall, E. Nat. Genet. (1994) [Pubmed]
  2. Inhibition of apoptosis improves outcome in a model of congenital muscular dystrophy. Girgenrath, M., Dominov, J.A., Kostek, C.A., Miller, J.B. J. Clin. Invest. (2004) [Pubmed]
  3. Deficiency of merosin in dystrophic dy mice and genetic linkage of laminin M chain gene to dy locus. Sunada, Y., Bernier, S.M., Kozak, C.A., Yamada, Y., Campbell, K.P. J. Biol. Chem. (1994) [Pubmed]
  4. Electrotransfer of naked DNA in the skeletal muscles of animal models of muscular dystrophies. Vilquin, J.T., Kennel, P.F., Paturneau-Jouas, M., Chapdelaine, P., Boissel, N., Delaère, P., Tremblay, J.P., Scherman, D., Fiszman, M.Y., Schwartz, K. Gene Ther. (2001) [Pubmed]
  5. Sternohyoid muscle fatigue properties of dy/dy dystrophic mice, an animal model of merosin-deficient congenital muscular dystrophy. van Lunteren, E., Moyer, M. Pediatr. Res. (2003) [Pubmed]
  6. Hearing loss in the laminin-deficient dy mouse model of congenital muscular dystrophy. Pillers, D.A., Kempton, J.B., Duncan, N.M., Pang, J., Dwinnell, S.J., Trune, D.R. Mol. Genet. Metab. (2002) [Pubmed]
  7. Neural targeting of Mycobacterium leprae mediated by the G domain of the laminin-alpha2 chain. Rambukkana, A., Salzer, J.L., Yurchenco, P.D., Tuomanen, E.I. Cell (1997) [Pubmed]
  8. Merosin-deficient congenital muscular dystrophy. Partial genetic correction in two mouse models. Kuang, W., Xu, H., Vachon, P.H., Liu, L., Loechel, F., Wewer, U.M., Engvall, E. J. Clin. Invest. (1998) [Pubmed]
  9. Integrins (alpha7beta1) in muscle function and survival. Disrupted expression in merosin-deficient congenital muscular dystrophy. Vachon, P.H., Xu, H., Liu, L., Loechel, F., Hayashi, Y., Arahata, K., Reed, J.C., Wewer, U.M., Engvall, E. J. Clin. Invest. (1997) [Pubmed]
  10. Animal models for muscular dystrophy show different patterns of sarcolemmal disruption. Straub, V., Rafael, J.A., Chamberlain, J.S., Campbell, K.P. J. Cell Biol. (1997) [Pubmed]
  11. Altered expression of the alpha7beta1 integrin in human and murine muscular dystrophies. Hodges, B.L., Hayashi, Y.K., Nonaka, I., Wang, W., Arahata, K., Kaufman, S.J. J. Cell. Sci. (1997) [Pubmed]
  12. The mer receptor tyrosine kinase: expression and function suggest a role in innate immunity. Behrens, E.M., Gadue, P., Gong, S.Y., Garrett, S., Stein, P.L., Cohen, P.L. Eur. J. Immunol. (2003) [Pubmed]
  13. Muscle-specific BCL2 expression ameliorates muscle disease in laminin {alpha}2-deficient, but not in dystrophin-deficient, mice. Dominov, J.A., Kravetz, A.J., Ardelt, M., Kostek, C.A., Beermann, M.L., Miller, J.B. Hum. Mol. Genet. (2005) [Pubmed]
  14. Laminin alpha2 is essential for odontoblast differentiation regulating dentin sialoprotein expression. Yuasa, K., Fukumoto, S., Kamasaki, Y., Yamada, A., Fukumoto, E., Kanaoka, K., Saito, K., Harada, H., Arikawa-Hirasawa, E., Miyagoe-Suzuki, Y., Takeda, S., Okamoto, K., Kato, Y., Fujiwara, T. J. Biol. Chem. (2004) [Pubmed]
  15. Assignment of laminin alpha 2-chain gene (Lama2) to mouse chromosome 10A4-B1 by fluorescence in situ hybridization. Sallinen, R., Kuang, W., Engvall, E., Palotie, A., Wessman, M., Horelli-Kuitunen, N. Cytogenet. Cell Genet. (1999) [Pubmed]
  16. Tissue distribution of the dystrophin-related gene product and expression in the mdx and dy mouse. Love, D.R., Morris, G.E., Ellis, J.M., Fairbrother, U., Marsden, R.F., Bloomfield, J.F., Edwards, Y.H., Slater, C.P., Parry, D.J., Davies, K.E. Proc. Natl. Acad. Sci. U.S.A. (1991) [Pubmed]
  17. Integrin-linked kinase is required for laminin-2-induced oligodendrocyte cell spreading and CNS myelination. Chun, S.J., Rasband, M.N., Sidman, R.L., Habib, A.A., Vartanian, T. J. Cell Biol. (2003) [Pubmed]
  18. Muscular dystrophy by merosin deficiency decreases acetylcholinesterase activity in thymus of Lama2dy mice. Nieto-Cerón, S., del Campo, L.F., Muñoz-Delgado, E., Vidal, C.J., Campoy, F.J. J. Neurochem. (2005) [Pubmed]
  19. Merosin (laminin-2) localization in basal lamina of normal skeletal muscle fibers and changes in plasma membrane of merosin-deficient skeletal muscle fibers. Shibuya, S., Wakayama, Y., Inoue, M., Kojima, H., Oniki, H. Medical electron microscopy : official journal of the Clinical Electron Microscopy Society of Japan. (2003) [Pubmed]
  20. Dystroglycan is a binding protein of laminin and merosin in peripheral nerve. Yamada, H., Shimizu, T., Tanaka, T., Campbell, K.P., Matsumura, K. FEBS Lett. (1994) [Pubmed]
  21. Expression of merosin in the thymus and its interaction with thymocytes. Chang, A.C., Wadsworth, S., Coligan, J.E. J. Immunol. (1993) [Pubmed]
  22. Intraperitoneal administration of phosphorothioate antisense oligodeoxynucleotide against splicing enhancer sequence induced exon skipping in dystrophin mRNA expressed in mdx skeletal muscle. Takeshima, Y., Yagi, M., Wada, H., Matsuo, M. Brain Dev. (2005) [Pubmed]
  23. Laminin-induced acetylcholine receptor clustering: an alternative pathway. Sugiyama, J.E., Glass, D.J., Yancopoulos, G.D., Hall, Z.W. J. Cell Biol. (1997) [Pubmed]
  24. Differential heparin sensitivity of alpha-dystroglycan binding to laminins expressed in normal and dy/dy mouse skeletal muscle. McDearmon, E.L., Burwell, A.L., Combs, A.C., Renley, B.A., Sdano, M.T., Ervasti, J.M. J. Biol. Chem. (1998) [Pubmed]
  25. Laminin and alpha7beta1 integrin regulate agrin-induced clustering of acetylcholine receptors. Burkin, D.J., Kim, J.E., Gu, M., Kaufman, S.J. J. Cell. Sci. (2000) [Pubmed]
  26. Relationship between neuronal migration and cell-substratum adhesion: laminin and merosin promote olfactory neuronal migration but are anti-adhesive. Calof, A.L., Lander, A.D. J. Cell Biol. (1991) [Pubmed]
  27. Elimination of myostatin does not combat muscular dystrophy in dy mice but increases postnatal lethality. Li, Z.F., Shelton, G.D., Engvall, E. Am. J. Pathol. (2005) [Pubmed]
  28. ADAM12 overexpression does not improve outcome in mice with laminin alpha2-deficient muscular dystrophy. Guo, L.T., Shelton, G.D., Wewer, U.M., Engvall, E. Neuromuscul. Disord. (2005) [Pubmed]
  29. Immunogold and freeze etch electron microscopic studies of merosin localization in basal lamina of human skeletal muscle fibers. Wakayama, Y., Murahashi, M., Jimi, T., Kojima, H., Shibuya, S., Oniki, H. Acta Neuropathol. (1997) [Pubmed]
  30. Gene expression profiling of diaphragm muscle in alpha2-laminin (merosin)-deficient dy/dy dystrophic mice. van Lunteren, E., Moyer, M., Leahy, P. Physiol. Genomics (2006) [Pubmed]
  31. Partial laminin alpha2 chain restoration in alpha2 chain-deficient dy/dy mouse by primary muscle cell culture transplantation. Vilquin, J.T., Kinoshita, I., Roy, B., Goulet, M., Engvall, E., Tomé, F., Fardeau, M., Tremblay, J.P. J. Cell Biol. (1996) [Pubmed]
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