Biomaterial Database

The distribution of dystrophin in the murine central nervous system: an immunocytochemical study. 1993

H G Lidov, and T J Byers, and L M Kunkel

Department of Pathology and Neurology, Childrens Hospital Medical Center, Boston, MA 02115.

A mild non-progressive cognitive defect is a feature of the fatal X-linked disease, Duchenne muscular dystrophy. Recent studies have identified the genetic defect and the resulting loss of the protein dystrophin, and shown that dystrophin messenger RNA and protein are present in normal brain tissue. We have performed western immunoblotting and fluorescence immunocytochemistry using a sensitive antibody made against a large fragment of the dystrophin molecule to study the regional, cellular and subcellular distribution of dystrophin in the mammalian brain. The brains of B10 (control) and mdx (dystrophin deficient null mutant) mouse brain were compared on a point-by-point basis to verify that only dystrophin and not autosomal dystrophin related protein or cross-reacting proteins were being identified. In addition three murine neurologic mutants, nervous, lurcher, and weaver, were studied to refine the localization of dystrophin. In western immunoblots, dystrophin is present in all regions of the brain and in greatest abundance in the cerebellum. Dystrophin, as demonstrated in immunofluorescence, is present in neurons, but not in glia or myelin, and forms punctate foci associated with the plasma membrane of perikarya and dendrites, but not axons. While dystrophin is abundant in cerebral cortical neurons and cerebellar Purkinje cells, it is absent from most subcortical neurons, the granule cells of fascia dentata, and cerebellar neurons other than Purkinje cells. The absence of dystrophin in the cerebellum of the Purkinje cell deficient mutants nervous and lurcher, and its presence in the granule cell deficient mutant weaver indicate that dystrophin is a component of Purkinje cells rather than closely apposed afferents to those cells. The distribution and localization of dystrophin suggests a role in organizing the plasma membrane, possibly as an anchor of the postsynaptic apparatus, a possible basis for the cognitive defect in Duchenne dystrophy.

UI	MeSH Term	Description	Entries
D008817	Mice, Mutant Strains	Mice bearing mutant genes which are phenotypically expressed in the animals.	Mouse, Mutant Strain,Mutant Mouse Strain,Mutant Strain of Mouse,Mutant Strains of Mice,Mice Mutant Strain,Mice Mutant Strains,Mouse Mutant Strain,Mouse Mutant Strains,Mouse Strain, Mutant,Mouse Strains, Mutant,Mutant Mouse Strains,Mutant Strain Mouse,Mutant Strains Mice,Strain Mouse, Mutant,Strain, Mutant Mouse,Strains Mice, Mutant,Strains, Mutant Mouse
D008818	Mice, Neurologic Mutants	Mice which carry mutant genes for neurologic defects or abnormalities.	Lurcher Mice,Nervous Mice,Reeler Mice,Staggerer Mice,Weaver Mice,Chakragati Mice,Chakragati Mouse,Lurcher Mouse,Mice, Neurological Mutants,Mouse, Neurologic Mutant,Mouse, Neurological Mutant,Nervous Mouse,Neurologic Mutant Mice,Neurological Mutant Mouse,Reeler Mouse,Staggerer Mouse,Weaver Mouse,ckr Mutant Mice,Mice, Chakragati,Mice, Lurcher,Mice, Nervous,Mice, Neurologic Mutant,Mice, Reeler,Mice, Staggerer,Mice, Weaver,Mice, ckr Mutant,Mouse, Chakragati,Mouse, Lurcher,Mouse, Nervous,Mouse, Reeler,Mouse, Staggerer,Mouse, Weaver,Mutant Mice, Neurologic,Mutant Mice, ckr,Mutant Mouse, Neurologic,Neurologic Mutant Mouse
D001921	Brain	The part of CENTRAL NERVOUS SYSTEM that is contained within the skull (CRANIUM). Arising from the NEURAL TUBE, the embryonic brain is comprised of three major parts including PROSENCEPHALON (the forebrain); MESENCEPHALON (the midbrain); and RHOMBENCEPHALON (the hindbrain). The developed brain consists of CEREBRUM; CEREBELLUM; and other structures in the BRAIN STEM.	Encephalon
D005455	Fluorescent Antibody Technique	Test for tissue antigen using either a direct method, by conjugation of antibody with fluorescent dye (FLUORESCENT ANTIBODY TECHNIQUE, DIRECT) or an indirect method, by formation of antigen-antibody complex which is then labeled with fluorescein-conjugated anti-immunoglobulin antibody (FLUORESCENT ANTIBODY TECHNIQUE, INDIRECT). The tissue is then examined by fluorescence microscopy.	Antinuclear Antibody Test, Fluorescent,Coon's Technique,Fluorescent Antinuclear Antibody Test,Fluorescent Protein Tracing,Immunofluorescence Technique,Coon's Technic,Fluorescent Antibody Technic,Immunofluorescence,Immunofluorescence Technic,Antibody Technic, Fluorescent,Antibody Technics, Fluorescent,Antibody Technique, Fluorescent,Antibody Techniques, Fluorescent,Coon Technic,Coon Technique,Coons Technic,Coons Technique,Fluorescent Antibody Technics,Fluorescent Antibody Techniques,Fluorescent Protein Tracings,Immunofluorescence Technics,Immunofluorescence Techniques,Protein Tracing, Fluorescent,Protein Tracings, Fluorescent,Technic, Coon's,Technic, Fluorescent Antibody,Technic, Immunofluorescence,Technics, Fluorescent Antibody,Technics, Immunofluorescence,Technique, Coon's,Technique, Fluorescent Antibody,Technique, Immunofluorescence,Techniques, Fluorescent Antibody,Techniques, Immunofluorescence,Tracing, Fluorescent Protein,Tracings, Fluorescent Protein
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D014018	Tissue Distribution	Accumulation of a drug or chemical substance in various organs (including those not relevant to its pharmacologic or therapeutic action). This distribution depends on the blood flow or perfusion rate of the organ, the ability of the drug to penetrate organ membranes, tissue specificity, protein binding. The distribution is usually expressed as tissue to plasma ratios.	Distribution, Tissue,Distributions, Tissue,Tissue Distributions
D015151	Immunoblotting	Immunologic method used for detecting or quantifying immunoreactive substances. The substance is identified by first immobilizing it by blotting onto a membrane and then tagging it with labeled antibodies.	Dot Immunoblotting,Electroimmunoblotting,Immunoelectroblotting,Reverse Immunoblotting,Immunoblotting, Dot,Immunoblotting, Reverse,Dot Immunoblottings,Electroimmunoblottings,Immunoblottings,Immunoblottings, Dot,Immunoblottings, Reverse,Immunoelectroblottings,Reverse Immunoblottings
D016189	Dystrophin	A muscle protein localized in surface membranes which is the product of the Duchenne/Becker muscular dystrophy gene. Individuals with Duchenne muscular dystrophy usually lack dystrophin completely while those with Becker muscular dystrophy have dystrophin of an altered size. It shares features with other cytoskeletal proteins such as SPECTRIN and alpha-actinin but the precise function of dystrophin is not clear. One possible role might be to preserve the integrity and alignment of the plasma membrane to the myofibrils during muscle contraction and relaxation. MW 400 kDa.
D051379	Mice	The common name for the genus Mus.	Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus