Hearing loss in the laminin-deficient dy mouse model of congenital muscular dystrophy

Pillers, De Ann M.; Kempton, J. Beth; Duncan, Nancy M.; Pang, Jiaqing; Dwinnell, Shannon J.; Trune, Dennis R.

doi:10.1016/s1096-7192(02)00039-2

Cited by 23 publications

(21 citation statements)

References 38 publications

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“…13,24,33,34,91 Although beyond the scope of the current study, it will be of interest to determine the extent to which Galgt2 overexpression will affect other cells and tissues where pathology exists in dy animals. For example, laminin ␣2-deficient mice have peripheral neuropathy, 92 sensorineural hearing loss, 93 aberrant myelination, 94,95 and defects in synaptic plasticity, 96 thymocyte, 97 and testicular development. 42 These findings show laminin ␣2 mediates many developmental processes in addition to maintenance of muscle membrane integrity.…”

Section: Discussionmentioning

confidence: 99%

Overexpression of the Cytotoxic T Cell (CT) Carbohydrate Inhibits Muscular Dystrophy in the dyW Mouse Model of Congenital Muscular Dystrophy 1A

Chandrasekharan²,

Yoon³

et al. 2007

The American Journal of Pathology

108

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A number of recent studies have demonstrated therapeutic effects of transgenes on the development of muscle pathology in the mdx mouse model for Duchenne muscular dystrophy, but none have been shown also to be effective in mouse models for laminin ␣2-deficient congenital muscular dystrophy (MDC1A). Here, we show that overexpression of the cytotoxic T cell (CT) GalNAc transferase (Galgt2) is effective in inhibiting the development of muscle pathology in the dy W mouse model of MDC1A, much as we had previously shown in mdx animals. Embryonic overexpression of Galgt2 in skeletal muscles using transgenic mice or postnatal overexpression using adenoassociated virus both reduced the extent of muscle pathology in dy W /dy W skeletal muscle. As with mdx mice, embryonic overexpression of the Galgt2 transgene in dy W /dy W myofibers inhibited muscle growth, whereas postnatal overexpression did not. Both embryonic and postnatal overexpression of Galgt2 in dy W /dy W muscle increased the expression of agrin, a protein that, in recombinant form, has been shown to ameliorate disease, whereas laminin ␣1, another disease modifier, was not expressed. Galgt2 overexpression also stimulated the glycosylation of a glycolipid with the CT carbohydrate, and glycolipids accounted for most of the CT-reactive material in postnatal overexpression experiments. These experiments demonstrate that Galgt2 overexpression is effective in altering disease progression in skeletal muscles of dy W mice and should be considered as a therapeutic target in

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Section: Discussionmentioning

confidence: 99%

Overexpression of the Cytotoxic T Cell (CT) Carbohydrate Inhibits Muscular Dystrophy in the dyW Mouse Model of Congenital Muscular Dystrophy 1A

Chandrasekharan²,

Yoon³

et al. 2007

The American Journal of Pathology

108

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“…Type IV collagen was absent from the inner ear in a canine model of X-linked Alport syndrome, 37 and sensorineural hearing loss has also been linked to a defect in the laminin ␣2 chain in mice. 38 Laminin 11 is found in the basilar membrane in humans. 39 To our knowledge CD151 has not been described in the inner ear, but our results suggest it may be important for ECM assembly in this organ.…”

Section: Discussionmentioning

confidence: 99%

CD151, the first member of the tetraspanin (TM4) superfamily detected on erythrocytes, is essential for the correct assembly of human basement membranes in kidney and skin

Crew

Burton

Kagan

et al. 2004

Blood

233

139

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Tetraspanins are thought to facilitate the formation of multiprotein complexes at cell surfaces, but evidence illuminating the biologic importance of this role is sparse. Tetraspanin CD151 forms very stable laminin-binding complexes with integrins alpha3beta1 and alpha6beta1 in kidney and alpha3beta1 and alpha6beta4 in skin. It is encoded by a gene at the same position on chromosome 11p15.5 as the MER2 blood group gene. We show that CD151 expresses the MER2 blood group antigen and is located on erythrocytes. We examined CD151 in 3 MER2-negative patients (2 are sibs) of Indian Jewish origin with end-stage kidney disease. In addition to hereditary nephritis the sibs have sensorineural deafness, pretibial epidermolysis bullosa, and beta-thalassemia minor. The 3 patients are homozygous for a single nucleotide insertion (G383) in exon 5 of CD151, causing a frameshift and premature stop signal at codon 140. The resultant truncated protein would lack its integrin-binding domain. We conclude that CD151 is essential for the proper assembly of the glomerular and tubular basement membrane in kidney, has functional significance in the skin, is probably a component of the inner ear, and could play a role in erythropoiesis.

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“…No epiblast differentiation (Scheele et al 2005) α2 Dy (unknown spontaneous mutation) Lethal within 6 months of age. Moderate muscular dystrophy, peripheral neuropathy (Xu et al 1994a;Sunada et al 1994), hearing loss (Pillers et al 2002), and aberrant thymocyte development (Wagner et al 2000) α2…”

Section: Concluding Remarks and Future Perspectivesmentioning

confidence: 99%

Laminins

2009

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Laminins are cell adhesion molecules that comprise a family of glycoproteins found predominantly in basement membranes, which are the thin sheets of extracellular matrix that underlie epithelial and endothelial cells and surround muscle cells, Schwann cells, and fat cells. Many laminins self-assemble to form networks that remain in close association with cells through interactions with cell surface receptors. Laminins are vital for many physiological functions. They are essential for early embryonic development and organogenesis and have crucial functions in several tissues including muscle, nerve, skin, kidney, lung, and the vasculature. A great wealth of data on laminins is available, and an in-depth description is not attempted here. In this review, I will instead provide a snapshot of laminin structure, tissue distribution, and interactions with other matrix molecules and receptors and briefly describe laminin mutations in mice and humans. Several illuminating and timely reviews are cited that can be consulted for references to original articles and more detailed information concerning laminins.

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Hearing loss in the laminin-deficient dy mouse model of congenital muscular dystrophy

Cited by 23 publications

References 38 publications

Overexpression of the Cytotoxic T Cell (CT) Carbohydrate Inhibits Muscular Dystrophy in the dyW Mouse Model of Congenital Muscular Dystrophy 1A

Overexpression of the Cytotoxic T Cell (CT) Carbohydrate Inhibits Muscular Dystrophy in the dyW Mouse Model of Congenital Muscular Dystrophy 1A

CD151, the first member of the tetraspanin (TM4) superfamily detected on erythrocytes, is essential for the correct assembly of human basement membranes in kidney and skin

Laminins

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