Manipulation of genes in the mouse genome to produce transgenic or gene-targeted animals represents a powerful experimental tool to study the role of specific gene products in complex physiological systems. Because of the power of studying genetically altered mice, many laboratori ...
Over the past decades, transgenic mice have become a valuable tool in investigating gene expression, regulation, and function. Mouse models have been established for various human diseases to determine gene expression patterns and to elucidate gene function in tissues and organ syste ...
The ability to alter the mouse genome through homologous recombination in their embryonic stem (ES) cells, and propagate the modification through their germ-line, has revolutionized biomedical research. Such gene-targeted mice have afforded researchers unprecedented oppo ...
Immunocytochemical procedures offer a unique means to visualize receptors at cellular and subcellular resolution. This approach has been enhanced by the availability of immunochemical probes to simultaneously visualize cellular ultrastructure, such as intracellular o ...
The advent of powerful molecular techniques to study protein structure and function allows the modification of the codmg region of genes to produce proteins with altered structures that can be studied for changes in biochemical properties. The most common way to do structure/function st ...
Heterotrimeric guanine nucleotide-binding regulatory (G) proteins, composed of α-, β-, and γ-subunits, play pivotal roles in many receptor-mediated transmembrane signaling processes. Although detailed regulatory modes of G protein-mediated signal transduction have not y ...
The demonstration that many intracellular signaling processes are mediated by a family of closely related guanine nucleotide binding proteins (G proteins) has led to the development of specific techniques that can be used to identify which of these polypeptide(s) is involved upon rece ...
The basic mechanism of G protein-mediated transmembrane signaling was elucidated in the late 1970s and early 1980s. Subsequently, molecular clomng has identified a large array of closely related receptors (R), G protein subunits (G), and effecters (E). Currently, an important research g ...
Heterologous expression of receptor proteins provides a means of studying a molecularly defined receptor subtype in isolation from species closely related either by function and/or homology. For example, metabotropic glutamate receptors (mGluRs) comprise a large family (pre ...
G proteins link heptahelical membrane receptors to their effector systems. The G proteins consist of three subunits, α, β, and γ, of which until now 23 (including splice variants), 6, and 11 different forms are known, respectively (for reviews, see refs. 1 and 2). By sequence homology of G protein α-subuni ...
Investigation of the function of intracellularly located protein components of receptor-effector transduction pathways has been hampered not only by their inaccessibility, but also by the lack of specific tools. The problem is particularly acute when the effect of interest must be m ...
Localization of receptors in brain sections using autoradtographlc detection of radioligand binding has been an important technique in the neuroanatomical identification of a large number of neurotransmitter receptors. However, receptor autoradiography provides lit ...
Neural stem cell (NSC) biology has generated a great deal of interest in recent years. It can inform on both intrinsic and extrinsic processes that underlie cell diversity within the central nervous system (CNS), and is a powerful method for improving understanding of cell ancestry and potenti ...
While still in its infancy, developments in the exciting field of cell replacement and gene transfer to the central nervous system (CNS) are providing the basis for potentially new and powerful therapeutic approaches to a wide range of neurological diseases. Neuronal replacement and par ...
Neural transplantation as a therapy for neurodegenerative diseases has received much attention over the past two decades. The possibility that disease progress could be arrested and function restored raised hopes that a new treatment, particularly for Parkinson’s disease (PD), was ...
The recent development of recombinant viral vectors that are capable of transducing postmitotic cells may provide a powerful new tool for studying brain function, as well as ameliorative strategies in models of neurological disease. Some of these vectors have recently demonstrated d ...
Since the advent of modern neurotransplantation research about two decades ago, considerable attention has focused on its potential use in the treatment of neurodegenerative disorders, particularly Parkinson’s disease. However, although clinical application is limited to a ...
The cell suspension grafting procedure, as originally described by (1983), has become the standard protocol for the implantation of fetal neuronal cell suspensions to deep brain nuclei. Its major advantages, compared to the earlier studies of transplanting solid pieces of fetal tissue ...
The blood-brain barrier (BBB) includes anatomical, physicochemical, and biochemical mechanisms that control the exchange of materials between blood and brain and cerebrospinal fluid (CSF). Thus two distinct systems, the BBB and the blood-CSF barrier systems, control cerebral ho ...
The tracer experiments of Reese and Karnovsky (1) demonstrated that it was the endothelium that formed a permeability barrier because electron-dense tracers such as horseradish peroxidase did not pass from the vessel lumen through the interendothelial cleft. The structure respon ...