La Jolla Cancer Research Foundation

Washington University

Eva Engvall

Ilmo Leivo

Erkki I Ruoslahti

Joshua R Sanes

Kurt R Gehlsen

Kiichi Arahata

This invention provides an isolated nucleic acid molecule encoding a subunit of a protein, the protein having an apparent molecular weight of about 800 kD, designated merosin. Also provided are isolated nucleic acid molecules which encode merosin fragments. Anti-merosin antibodies, vectors for the recombinant production of merosin, and the expression of recombinant proteins by use of a host vector system also are provided. The invention further provides the use of merosin to promote neurite growth and for certain diagnostic applications.

Nucleic acids encoding merosin

Merosin fragments and uses thereof

The present invention relates to a method for detecting altered expression or localization of a cytoskeleton/basal lamina protein in a tissue sample obtained from an individual, wherein the altered expression or localization are associated with a muscular dystrophy such as Fukuyama congenital muscular dystrophy (FCMD). The invention provides an immunohistochemical method for detecting the expression and localization in a tissue, such as muscle, of laminin M (merosin), which is a protein component of the basal lamina, wherein certain defined changes are diagnostic of individuals predisposed to FCMD. The invention also provides a prenatal diagnostic screening procedure, using a tissue such as placenta, wherein the screening procedure can identify an individual predisposed to FCMD. The invention further provides methods for identifying an individual predisposed to other muscular dystrophies such as Walker-Warburg Syndrome (WWS) and muscle-eye-brain disease of the Finnish type (MEB).

Changes in laminin subunit composition are diagnostic of Fukuyama

This invention provides a purified protein, having an apparent molecular weight of about 800 kDa, designated merosin. Also provided is an isolated nucleic acid sequence which encodes merosin. The invention further provides antibodies, vectors, and the expression of recombinant proteins by use of a host vector system. The invention also provides the use of merosin to promote neurite growth and for certain diagnostic applications.

A substantially pure heterotrimeric laminin variant comprising the structure M-X-B2, wherein M is the M polypeptide of merosin; X is selected from the group consisting of the B1 chain of laminin and S-laminin; and B2 is the B2 chain of laminin.

Merosin, nucleic acids encoding, fragments and uses thereof

An adhesion receptor for laminin is provided. The receptor is isolated from cell or tissue extracts and fractionated on an affinity column composed of cell attachment-promoting fragments of laminin coupled to Sepharose.TM. in the presence of divalent cations. This receptor can be used to prepare specific antibodies for the analysis of the amount of laminin receptor expressed by cells and has other applications in cellular and tumor biology.

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Rancho Santa Fe, CA, United States of America

Eva Engvall