{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T07:46:04Z","timestamp":1787471164995,"version":"build-2736575974"},"reference-count":44,"publisher":"The Company of Biologists","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2006,3,1]]},"abstract":"<jats:p>Pierson syndrome is a recently defined disease usually lethal within the first postnatal months and caused by mutations in the gene encoding laminin\u03b22 (LAMB2). The hallmarks of Pierson syndrome are congenital nephrotic syndrome accompanied by ocular abnormalities, including microcoria(small pupils), with muscular and neurological developmental defects also present. Lamb2-\/- mice are a model for Pierson syndrome;they exhibit defects in the kidney glomerular barrier, in the development and organization of the neuromuscular junction, and in the retina. Lamb2-\/- mice fail to thrive and die very small at 3 weeks of age, but to what extent the kidney and neuromuscular defects each contribute to this severe phenotype has been obscure, though highly relevant to understanding Pierson syndrome. To investigate this, we generated transgenic mouse lines expressing rat laminin \u03b22 either in muscle or in glomerular epithelial cells (podocytes) and crossed them onto the Lamb2-\/- background. Rat \u03b22 was confined in skeletal muscle to synapses and myotendinous junctions, and in kidney to the glomerular basement membrane. In transgenic Lamb2-\/- mice, \u03b22 deposition in only glomeruli prevented proteinuria but did not ameliorate the severe phenotype. By contrast, \u03b22 expression in only muscle restored synaptic architecture and led to greatly improved health, but the mice died from kidney disease at 1 month. Rescue of both glomeruli and synapses was associated with normal weight gain, fertility and lifespan. We conclude that muscle defects in Lamb2-\/- mice are responsible for the severe failure to thrive phenotype, and that renal replacement therapy alone will be an inadequate treatment for Pierson syndrome.<\/jats:p>","DOI":"10.1242\/dev.02270","type":"journal-article","created":{"date-parts":[[2006,2,1]],"date-time":"2006-02-01T20:23:08Z","timestamp":1138825388000},"page":"967-975","source":"Crossref","is-referenced-by-count":68,"title":["Transgenic isolation of skeletal muscle and kidney defects in laminin\u03b22 mutant mice: implications for Pierson syndrome"],"prefix":"10.1242","volume":"133","author":[{"given":"Jeffrey H.","family":"Miner","sequence":"first","affiliation":[{"name":"Renal Division, Washington University School of Medicine, St Louis, MO 63110,USA."},{"name":"Department of Cell Biology and Physiology, Washington University School of Medicine, St Louis, MO 63110, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gloriosa","family":"Go","sequence":"additional","affiliation":[{"name":"Renal Division, Washington University School of Medicine, St Louis, MO 63110,USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeanette","family":"Cunningham","sequence":"additional","affiliation":[{"name":"Renal Division, Washington University School of Medicine, St Louis, MO 63110,USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruce L.","family":"Patton","sequence":"additional","affiliation":[{"name":"CROET, Oregon Health Sciences University, Portland, OR 97239, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George","family":"Jarad","sequence":"additional","affiliation":[{"name":"Renal Division, Washington University School of Medicine, St Louis, MO 63110,USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","reference":[{"key":"2021042605412027900_REF1","doi-asserted-by":"crossref","unstructured":"Abrahamson, D. R. and Perry, E. W. (1986). Evidence for splicing new basement membrane into old during glomerular development in newborn rat kidneys. J. Cell Biol.103,2489-2498.","DOI":"10.1083\/jcb.103.6.2489"},{"key":"2021042605412027900_REF2","doi-asserted-by":"crossref","unstructured":"Abrahamson, D. R., Irwin, M. H., St John, P. L., Perry, E. W.,Accavitti, M. A., Heck, L. W. and Couchman, J. R. (1989). Selective immunoreactivities of kidney basement membranes to monoclonal antibodies against laminin: localization of the end of the long arm and the short arms to discrete microdomains. J. Cell Biol.109,3477-3491.","DOI":"10.1083\/jcb.109.6.3477"},{"key":"2021042605412027900_REF3","doi-asserted-by":"crossref","unstructured":"Aumailley, M., Bruckner-Tuderman, L., Carter, W. G., Deutzmann,R., Edgar, D., Ekblom, P., Engel, J., Engvall, E., Hohenester, E., Jones, J. C. R. et al. (2005). A simplified laminin nomenclature. Matrix Biol.24,326-332.","DOI":"10.1016\/j.matbio.2005.05.006"},{"key":"2021042605412027900_REF4","doi-asserted-by":"crossref","unstructured":"Burgeson, R. E. and Christiano, A. M. (1997). The dermal-epidermal junction. Curr. Opin. Cell Biol.9, 651-658.","DOI":"10.1016\/S0955-0674(97)80118-4"},{"key":"2021042605412027900_REF5","doi-asserted-by":"crossref","unstructured":"Eremina, V., Wong, M. A., Cui, S., Schwartz, L. and Quaggin, S. E. (2002). Glomerular-specific gene excision in vivo. J. Am. Soc. Nephrol.13,788-793.","DOI":"10.1681\/ASN.V133788"},{"key":"2021042605412027900_REF6","doi-asserted-by":"crossref","unstructured":"Green, T. L., Hunter, D. D., Chan, W., Merlie, J. P. and Sanes,J. R. (1992). Synthesis and assembly of the synaptic cleft protein S-laminin by cultured cells. J. Biol. Chem.267,2014-2022.","DOI":"10.1016\/S0021-9258(18)46047-4"},{"key":"2021042605412027900_REF7","unstructured":"Hasselbacher, K., Wiggins, R., Mucha, B., Hinkes, B., Pohl, M.,Zenker, M., Ozaltin, F., Bakkaloglu, A., Hagan, D. and Hildebrandt, F.(2005). Recessive mutations in LAMB2 as cause of congenital nephrotic syndrome (CNS). J. Am. Soc. Nephrol.16, 92A."},{"key":"2021042605412027900_REF8","doi-asserted-by":"crossref","unstructured":"Hunter, D. D., Shah, V., Merlie, J. P. and Sanes, J. R.(1989). A laminin-like adhesive protein concentrated in the synaptic cleft of the neuromuscular junction. Nature338,229-234.","DOI":"10.1038\/338229a0"},{"key":"2021042605412027900_REF9","doi-asserted-by":"crossref","unstructured":"Jaynes, J. B., Johnson, J. E., Buskin, J. N., Gartside, C. L. and Hauschka, S. D. (1988). The muscle creatine kinase gene is regulated by multiple upstream elements, including a muscle-specific enhancer. Mol. Cell. Biol.8, 62-70.","DOI":"10.1128\/MCB.8.1.62"},{"key":"2021042605412027900_REF10","doi-asserted-by":"crossref","unstructured":"Johnson, J. E., Wold, B. J. and Hauschka, S. D.(1989). Muscle creatine kinase sequence elements regulating skeletal and cardiac muscle expression in transgenic mice. Mol. Cell. Biol.9,3393-3399.","DOI":"10.1128\/MCB.9.8.3393"},{"key":"2021042605412027900_REF11","doi-asserted-by":"crossref","unstructured":"Kashtan, C. E. (2004). Familial hematuria due to type IV collagen mutations: Alport syndrome and thin basement membrane nephropathy. Curr. Opin. Pediatr.16,177-181.","DOI":"10.1097\/00008480-200404000-00011"},{"key":"2021042605412027900_REF12","doi-asserted-by":"crossref","unstructured":"Kestila, M., Lenkkeri, U., Mannikko, M., Lamerdin, J., McCready,P., Putaala, H., Ruotsalainen, V., Morita, T., Nissinen, M., Herva, R. et al. (1998). Positionally cloned gene for a novel glomerular protein - nephrin - is mutated in congenital nephrotic syndrome. Mol. Cell1,575-582.","DOI":"10.1016\/S1097-2765(00)80057-X"},{"key":"2021042605412027900_REF13","doi-asserted-by":"crossref","unstructured":"Kikkawa, Y., Virtanen, I. and Miner, J. H.(2003). Mesangial cells organize the glomerular capillaries by adhering to the G domain of laminin alpha5 in the glomerular basement membrane. J. Cell Biol.161,187-196.","DOI":"10.1083\/jcb.200211121"},{"key":"2021042605412027900_REF14","doi-asserted-by":"crossref","unstructured":"Knight, D., Tolley, L. K., Kim, D. K., Lavidis, N. A. and Noakes, P. G. (2003). Functional analysis of neurotransmission at beta2-laminin deficient terminals. J. Physiol.546,789-800.","DOI":"10.1113\/jphysiol.2002.030924"},{"key":"2021042605412027900_REF15","unstructured":"Kuang, W., Xu, H., Vachon, P. H., Liu, L., Loechel, F., Wewer,U. M. and Engvall, E. (1998). Merosin-deficient congenital muscular dystrophy. Partial genetic correction in two mouse models. J. Clin. Invest.102,844-852."},{"key":"2021042605412027900_REF16","doi-asserted-by":"crossref","unstructured":"Libby, R. T., Xu, Y., Selfors, L. M., Brunken, W. J. and Hunter,D. D. (1997). Identification of the cellular source of laminin beta2 in adult and developing vertebrate retinae. J. Comp. Neurol.389,655-667.","DOI":"10.1002\/(SICI)1096-9861(19971229)389:4<655::AID-CNE8>3.0.CO;2-#"},{"key":"2021042605412027900_REF17","doi-asserted-by":"crossref","unstructured":"Libby, R. T., Lavallee, C. R., Balkema, G. W., Brunken, W. J. and Hunter, D. D. (1999). Disruption of laminin beta2 chain production causes alterations in morphology and function in the CNS. J. Neurosci.19,9399-9411.","DOI":"10.1523\/JNEUROSCI.19-21-09399.1999"},{"key":"2021042605412027900_REF18","doi-asserted-by":"crossref","unstructured":"Libby, R. T., Champliaud, M. F., Claudepierre, T., Xu, Y.,Gibbons, E. P., Koch, M., Burgeson, R. E., Hunter, D. D. and Brunken, W. J. (2000). Laminin expression in adult and developing retinae: evidence of two novel CNS laminins. J. Neurosci.20,6517-6528.","DOI":"10.1523\/JNEUROSCI.20-17-06517.2000"},{"key":"2021042605412027900_REF19","doi-asserted-by":"crossref","unstructured":"Martin, P. T., Ettinger, A. J. and Sanes, J. R.(1995). A synaptic localization domain in the synaptic cleft protein, s-laminin\/laminin \u03b22. Science269,413-416.","DOI":"10.1126\/science.7618109"},{"key":"2021042605412027900_REF20","doi-asserted-by":"crossref","unstructured":"Miner, J. H. and Sanes, J. R. (1994). Collagen IV \u03b13, \u03b14, and \u03b15 chains in rodent basal laminae: Sequence,distribution, association with laminins, and developmental switches. J. Cell Biol.127,879-891.","DOI":"10.1083\/jcb.127.3.879"},{"key":"2021042605412027900_REF21","doi-asserted-by":"crossref","unstructured":"Miner, J. H. and Yurchenco, P. D. (2004). Laminin functions in tissue morphogenesis. Annu. Rev. Cell Dev. Biol.20,255-284.","DOI":"10.1146\/annurev.cellbio.20.010403.094555"},{"key":"2021042605412027900_REF22","doi-asserted-by":"crossref","unstructured":"Miner, J. H., Patton, B. L., Lentz, S. I., Gilbert, D. J.,Snider, W. D., Jenkins, N. A., Copeland, N. G. and Sanes, J. R.(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.137,685-701.","DOI":"10.1083\/jcb.137.3.685"},{"key":"2021042605412027900_REF23","doi-asserted-by":"crossref","unstructured":"Miner, J. H., Li, C., Mudd, J. L., Go, G. and Sutherland, A. E. (2004). Compositional and structural requirements for laminin and basement membranes during mouse embryo implantation and gastrulation. Development131,2247-2256.","DOI":"10.1242\/dev.01112"},{"key":"2021042605412027900_REF24","doi-asserted-by":"crossref","unstructured":"Moscoso, L. M., Merlie, J. P. and Sanes, J. R.(1995). N-CAM, 43K-rapsyn, and S-laminin mRNAs are concentrated at synaptic sites in muscle fibers. Mol. Cell Neurosci.6,80-89.","DOI":"10.1006\/mcne.1995.1008"},{"key":"2021042605412027900_REF25","doi-asserted-by":"crossref","unstructured":"Nishimune, H., Sanes, J. R. and Carlson, S. S.(2004). A synaptic laminin-calcium channel interaction organizes active zones in motor nerve terminals. Nature432,580-587.","DOI":"10.1038\/nature03112"},{"key":"2021042605412027900_REF26","doi-asserted-by":"crossref","unstructured":"Noakes, P. G., Gautam, M., Mudd, J., Sanes, J. R. and Merlie, J. P. (1995a). Aberrant differentiation of neuromuscular junctions in mice lacking s-laminin\/laminin \u03b22. Nature374,258-262.","DOI":"10.1038\/374258a0"},{"key":"2021042605412027900_REF27","doi-asserted-by":"crossref","unstructured":"Noakes, P. G., Miner, J. H., Gautam, M., Cunningham, J. M.,Sanes, J. R. and Merlie, J. P. (1995b). The renal glomerulus of mice lacking s-laminin\/laminin \u03b22: nephrosis despite molecular compensation by laminin \u03b21. Nat. Genet.10,400-406.","DOI":"10.1038\/ng0895-400"},{"key":"2021042605412027900_REF28","doi-asserted-by":"crossref","unstructured":"Parsons, M. J., Pollard, S. M., Saude, L., Feldman, B.,Coutinho, P., Hirst, E. M. A. and Stemple, D. L. (2002). Zebrafish mutants identify an essential role for laminins in notochord formation. Development129,3137-3146.","DOI":"10.1242\/dev.129.13.3137"},{"key":"2021042605412027900_REF29","doi-asserted-by":"crossref","unstructured":"Patton, B. L. (2000). Laminins of the neuromuscular system. Microsc. Res. Tech.51,247-261.","DOI":"10.1002\/1097-0029(20001101)51:3<247::AID-JEMT5>3.0.CO;2-Z"},{"key":"2021042605412027900_REF30","doi-asserted-by":"crossref","unstructured":"Patton, B. L., Miner, J. H., Chiu, A. Y. and Sanes, J. R.(1997). Distribution and function of laminins in the neuromuscular system of developing, adult, and mutant mice. J. Cell Biol.139,1507-1521.","DOI":"10.1083\/jcb.139.6.1507"},{"key":"2021042605412027900_REF31","doi-asserted-by":"crossref","unstructured":"Patton, B. L., Chiu, A. Y. and Sanes, J. R.(1998). Synaptic laminin prevents glial entry into the synaptic cleft. Nature393,698-701.","DOI":"10.1038\/31502"},{"key":"2021042605412027900_REF32","doi-asserted-by":"crossref","unstructured":"Sanes, J. R., Engvall, E., Butkowski, R. and Hunter, D. D.(1990). Molecular heterogeneity of basal laminae: Isoforms of laminin and collagen IV at the neuromuscular junction and elsewhere. J. Cell Biol.111,1685-1699.","DOI":"10.1083\/jcb.111.4.1685"},{"key":"2021042605412027900_REF33","doi-asserted-by":"crossref","unstructured":"Sasaki, T., Mann, K., Miner, J. H., Miosge, N. and Timpl, R.(2002). Domain IV of mouse laminin \u03b21 and \u03b22 chains:structure, glycosaminoglycan modification and immunochemical analysis of tissue contents. Eur. J. Biochem.269,431-442.","DOI":"10.1046\/j.0014-2956.2001.02663.x"},{"key":"2021042605412027900_REF34","doi-asserted-by":"crossref","unstructured":"Sasaki, T., Fassler, R. and Hohenester, E.(2004). Laminin: the crux of basement membrane assembly. J. Cell Biol.164,959-963.","DOI":"10.1083\/jcb.200401058"},{"key":"2021042605412027900_REF35","doi-asserted-by":"crossref","unstructured":"Smyth, N., Vatansever, H. S., Murray, P., Meyer, M., Frie, C.,Paulsson, M. and 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.144,151-160.","DOI":"10.1083\/jcb.144.1.151"},{"key":"2021042605412027900_REF36","doi-asserted-by":"crossref","unstructured":"St John, P. L. and Abrahamson, D. R. (2001). Glomerular endothelial cells and podocytes jointly synthesize laminin-1 and-11 chains. Kidney Int.60,1037-1046.","DOI":"10.1046\/j.1523-1755.2001.0600031037.x"},{"key":"2021042605412027900_REF37","unstructured":"St John, P. L., Wang, R., Yin, Y., Miner, J. H., Robert, B. and Abrahamson, D. R. (2001). Glomerular laminin isoform transitions: errors in metanephric culture are corrected by grafting. Am. J. Physiol. Renal Physiol.280,F695-F705."},{"key":"2021042605412027900_REF38","doi-asserted-by":"crossref","unstructured":"Straub, V., Rafael, J. A., Chamberlain, J. S. and Campbell, K. P. (1997). Animal models for muscular dystrophy show different patterns of sarcolemmal disruption. J. Cell Biol.139,375-385.","DOI":"10.1083\/jcb.139.2.375"},{"key":"2021042605412027900_REF39","doi-asserted-by":"crossref","unstructured":"Suzuki, O. T., Sertie, A. L., Der Kaloustian, V. M., Kok, F.,Carpenter, M., Murray, J., Czeizel, A. E., Kliemann, S. E., Rosemberg, S.,Monteiro, M. et al. (2002). Molecular analysis of collagen XVIII reveals novel mutations, presence of a third isoform, and possible genetic heterogeneity in Knobloch syndrome. Am. J. Hum. Genet.71,1320-1329.","DOI":"10.1086\/344695"},{"key":"2021042605412027900_REF40","unstructured":"Wewer, U. M., Thornell, L. E., Loechel, F., Zhang, X., Durkin,M. E., Amano, S., Burgeson, R. E., Engvall, E., Albrechtsen, R. and Virtanen,I. (1997). Extrasynaptic location of laminin beta 2 chain in developing and adult human skeletal muscle. Am. J. Pathol.151,621-631."},{"key":"2021042605412027900_REF41","doi-asserted-by":"crossref","unstructured":"Yurchenco, P. D., Amenta, P. S. and Patton, B. L.(2004). Basement membrane assembly, stability and activities observed through a developmental lens. Matrix Biol.22,521-538.","DOI":"10.1016\/j.matbio.2003.10.006"},{"key":"2021042605412027900_REF42","doi-asserted-by":"crossref","unstructured":"Zenker, M., Aigner, T., Wendler, O., Tralau, T., Muntefering,H., Fenski, R., Pitz, S., Schumacher, V., Royer-Pokora, B., Wuhl, E. et al. (2004a). Human laminin beta2 deficiency causes congenital nephrosis with mesangial sclerosis and distinct eye abnormalities. Hum. Mol. Genet.13,2625-2632.","DOI":"10.1093\/hmg\/ddh284"},{"key":"2021042605412027900_REF43","doi-asserted-by":"crossref","unstructured":"Zenker, M., Tralau, T., Lennert, T., Pitz, S., Mark, K., Madlon,H., Dotsch, J., Reis, A., Muntefering, H. and Neumann, L. M.(2004b). Congenital nephrosis, mesangial sclerosis, and distinct eye abnormalities with microcoria: an autosomal recessive syndrome. Am. J. Med. Genet. A130,138-145.","DOI":"10.1002\/ajmg.a.30310"},{"key":"2021042605412027900_REF44","doi-asserted-by":"crossref","unstructured":"Zenker, M., Pierson, M., Jonveaux, P. and Reis, A.(2005). Demonstration of two novel LAMB2 mutations in the original Pierson syndrome family reported 42 years ago. Am. J. Med. Genet. A138,73-74.","DOI":"10.1002\/ajmg.a.30894"}],"container-title":["Development"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/journals.biologists.com\/dev\/article-pdf\/133\/5\/967\/1517589\/967.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/journals.biologists.com\/dev\/article-pdf\/133\/5\/967\/1517589\/967.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,5,6]],"date-time":"2023-05-06T06:46:39Z","timestamp":1683355599000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.biologists.com\/dev\/article\/133\/5\/967\/43471\/Transgenic-isolation-of-skeletal-muscle-and-kidney"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2006,3,1]]},"references-count":44,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2006,3,1]]}},"URL":"https:\/\/doi.org\/10.1242\/dev.02270","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.10159.467649","asserted-by":"object"}]},"ISSN":["1477-9129","0950-1991"],"issn-type":[{"value":"1477-9129","type":"electronic"},{"value":"0950-1991","type":"print"}],"subject":[],"published":{"date-parts":[[2006,3,1]]}}}