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DAB1
The Disabled-1 (Dab1) gene encodes a key regulator of Reelin signaling. Reelin is a large glycoprotein secreted by neurons of the developing brain, particularly Cajal-Retzius cells. DAB1 functions downstream of Reln in a signaling pathway that controls cell positioning in the developing brain and during adult neurogenesis. It docks to the intracellular part of the Reelin very low density lipoprotein receptor (VLDLR) and apoE receptor type 2 (ApoER2) and becomes tyrosine-phosphorylated following binding of Reelin to cortical neurons. In mice, mutations of Dab1 and Reelin generate identical phenotypes. In humans, Reelin mutations are associated with brain malformations and mental retardation. In mice, Dab1 mutation results in the ''scrambler'' mouse phenotype. With a genomic length of 1.1 Mbp for a coding region of 5.5 kb, DAB1 provides a rare example of genomic complexity, which will impede the identification of human mutations. Gene function Cortical neurons form in specialize ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Reelin
Reelin, encoded by the ''RELN'' gene, is a large secreted extracellular matrix glycoprotein that helps regulate processes of neuronal migration and positioning in the developing brain by controlling cell–cell interactions. Besides this important role in early development, reelin continues to work in the adult brain. It modulates synaptic plasticity by enhancing the induction and maintenance of long-term potentiation. It also stimulates dendrite and dendritic spine development and regulates the continuing migration of neuroblasts generated in adult neurogenesis sites like the subventricular and subgranular zones. It is found not only in the brain but also in the liver, thyroid gland, adrenal gland, Fallopian tube, breast and in comparatively lower levels across a range of anatomical regions. Reelin has been suggested to be implicated in pathogenesis of several brain diseases. The expression of the protein has been found to be significantly lower in schizophrenia and psycho ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
VLDL Receptor
The very-low-density-lipoprotein receptor (VLDLR) is a transmembrane lipoprotein receptor of the low-density-lipoprotein (LDL) receptor family. VLDLR shows considerable homology with the members of this lineage. Discovered in 1992 by T. Yamamoto, VLDLR is widely distributed throughout the tissues of the body, including the heart, skeletal muscle, adipose tissue, and the brain, but is absent from the liver. This receptor has an important role in cholesterol uptake, metabolism of apolipoprotein E-containing triacylglycerol-rich lipoproteins, and neuronal migration in the developing brain. In humans, VLDLR is encoded by the ''VLDLR'' gene. Mutations of this gene may lead to a variety of symptoms and diseases, which include type I lissencephaly, cerebellar hypoplasia, and atherosclerosis. Protein structure VLDLR is a member of the low-density-lipoprotein (LDL) receptor family, which is entirely composed of type I transmembrane lipoprotein receptors. All members of this family share ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Scrambler Mouse
Scrambler is a spontaneous mouse mutant lacking a functional DAB1 gene, resulting in a phenotype resembling that seen in the reeler mouse. The strain was first described by Sweet ''et al.'' in 1996. Neuroanatomical abnormalities The spontaneous autosomal recessive scrambler mutation on chromosome 4 causes a deficiency of DAB1, encoding disabled-1, a protein involved in the signaling of the Reelin protein, lacking in the reeler mutant, Dab1-scm homozygous mutants possess a reeler-like phenotype with respect to cell malpositioning in cerebellar cortex, hippocampus, and neocortex. Purkinje cell and granule cell degeneration results in ataxia. Despite normal Reln mRNA levels, Dab1-scm mutants have defective reelin signaling, indicating that disabled-1 acts downstream of reelin. Cell ectopias are identical with targeted disruption of Dab1. Behavioral abnormalities Dab1-scm mutants have a widespread gait obvious to the naked eye (ataxia). In their home-cage, they often reel and fall, es ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Reeler
A reeler is a mouse mutant, so named because of its characteristic "reeling" gait. This is caused by the profound underdevelopment of the mouse's cerebellum, a segment of the brain responsible for locomotion. The mutation is autosomal and recessive, and prevents the typical cerebellar folia from forming. Cortical neurons are generated normally but are abnormally placed, resulting in disorganization of cortical laminar layers in the central nervous system. The reason is the lack of Reelin, an extracellular matrix glycoprotein, which, during the corticogenesis, is secreted mainly by the Cajal-Retzius cells. In the reeler neocortex, cortical plate neurons are aligned in a practically inverted fashion (‘‘outside-in’’). In the ventricular zone of the cortex fewer neurons have been found to have radial glial processes. In the dentate gyrus of hippocampus, no characteristic radial glial scaffold is formed and no compact granule cell layer is established. Therefore, the reeler m ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
ApoER2
Low-density lipoprotein receptor-related protein 8 (LRP8), also known as apolipoprotein E receptor 2 (ApoER2), is a protein that in humans is encoded by the ''LRP8'' gene. ApoER2 is a cell surface receptor that is part of the low-density lipoprotein receptor family. These receptors function in signal transduction and endocytosis of specific ligands. Through interactions with one of its ligands, reelin, ApoER2 plays an important role in embryonic neuronal migration and postnatal long-term potentiation. Another LDL family receptor, VLDLR, also interacts with reelin, and together these two receptors influence brain development and function. Decreased expression of ApoER2 is associated with certain neurological diseases. Structure ApoER2 is a protein made up of 870 amino acids. It is separated into a ligand binding domain of eight ligand binding regions, an EGF-like domain containing three cysteine-rich repeats, an O-linked glycosylation domain of 89 amino acids, a transmembrane ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Yotari
The yotari mouse is an autosomal recessive mutant. It has a mutated ''disabled homolog 1'' (Dab1) gene. This mutant mouse is recognized by unstable gait ("Yota-ru" in Japanese means "unstable gait") and tremor and by early deaths around the time of weaning. The cytoarchitectures of cerebellar and cerebral cortices and hippocampal formation of the yotari mouse are abnormal. These malformations resemble those of reeler A reeler is a mouse mutant, so named because of its characteristic "reeling" gait. This is caused by the profound underdevelopment of the mouse's cerebellum, a segment of the brain responsible for locomotion. The mutation is autosomal and recess ... mouse. References Molecular neuroscience Molecular genetics {{Neuroscience-stub ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Spinocerebellar Ataxia
Spinocerebellar ataxia (SCA) is a progressive, degenerative, genetic disease with multiple types, each of which could be considered a neurological condition in its own right. An estimated 150,000 people in the United States have a diagnosis of spinocerebellar ataxia at any given time. SCA is hereditary, progressive, degenerative, and often fatal. There is no known effective treatment or cure. SCA can affect anyone of any age. The disease is caused by either a recessive or dominant gene. In many cases people are not aware that they carry a relevant gene until they have children who begin to show signs of having the disorder. Signs and symptoms Spinocerebellar ataxia (SCA) is one of a group of genetic disorders characterized by slowly progressive incoordination of gait and is often associated with poor coordination of hands, speech, and eye movements. A review of different clinical features among SCA subtypes was recently published describing the frequency of non-cerebellar featu ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Upregulation
In the biological context of organisms' production of gene products, downregulation is the process by which a cell decreases the quantity of a cellular component, such as RNA or protein, in response to an external stimulus. The complementary process that involves increases of such components is called upregulation. An example of downregulation is the cellular decrease in the expression of a specific receptor in response to its increased activation by a molecule, such as a hormone or neurotransmitter, which reduces the cell's sensitivity to the molecule. This is an example of a locally acting (negative feedback) mechanism. An example of upregulation is the response of liver cells exposed to such xenobiotic molecules as dioxin. In this situation, the cells increase their production of cytochrome P450 enzymes, which in turn increases degradation of these dioxin molecules. Downregulation or upregulation of an RNA or protein may also arise by an epigenetic alteration. Such an epigene ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Gene Knockout
A gene knockout (abbreviation: KO) is a genetic technique in which one of an organism's genes is made inoperative ("knocked out" of the organism). However, KO can also refer to the gene that is knocked out or the organism that carries the gene knockout. Knockout organisms or simply knockouts are used to study gene function, usually by investigating the effect of gene loss. Researchers draw inferences from the difference between the knockout organism and normal individuals. The KO technique is essentially the opposite of a gene knock-in. Knocking out two genes simultaneously in an organism is known as a double knockout (DKO). Similarly the terms triple knockout (TKO) and quadruple knockouts (QKO) are used to describe three or four knocked out genes, respectively. However, one needs to distinguish between heterozygous and homozygous KOs. In the former, only one of two gene copies (alleles) is knocked out, in the latter both are knocked out. Methods Knockouts are accomplished throu ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Purkinje Cell
Purkinje cells, or Purkinje neurons, are a class of GABAergic inhibitory neurons located in the cerebellum. They are named after their discoverer, Czech people, Czech anatomist Jan Evangelista Purkyně, who characterized the cells in 1839. Structure These Cell (biology), cells are some of the largest neurons in the human brain (Betz cells being the largest), with an intricately elaborate dendrite, dendritic arbor, characterized by a large number of dendritic spines. Purkinje cells are found within the Cerebellum#Microanatomy, Purkinje layer in the cerebellum. Purkinje cells are aligned like dominos stacked one in front of the other. Their large dendritic arbors form nearly two-dimensional layers through which parallel fibers from the deeper-layers pass. These parallel fibers make relatively weaker excitatory synapse, excitatory (glutamatergic) synapses to spines in the Purkinje cell dendrite, whereas climbing fibers originating from the inferior olivary nucleus in the medull ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Tyrosine Kinase
A tyrosine kinase is an enzyme that can transfer a phosphate group from ATP to the tyrosine residues of specific proteins inside a cell. It functions as an "on" or "off" switch in many cellular functions. Tyrosine kinases belong to a larger class of enzymes known as protein kinases which also attach phosphates to other amino acids such as serine and threonine. Phosphorylation of proteins by kinases is an important mechanism for communicating signals within a cell (signal transduction) and regulating cellular activity, such as cell division. Protein kinases can become mutated, stuck in the "on" position, and cause unregulated growth of the cell, which is a necessary step for the development of cancer. Therefore, kinase inhibitors, such as imatinib and osimertinib, are often effective cancer treatments. Most tyrosine kinases have an associated protein tyrosine phosphatase, which removes the phosphate group. Reaction Protein kinases are a group of enzymes that possess a catal ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Cerebellum
The cerebellum (Latin for "little brain") is a major feature of the hindbrain of all vertebrates. Although usually smaller than the cerebrum, in some animals such as the mormyrid fishes it may be as large as or even larger. In humans, the cerebellum plays an important role in motor control. It may also be involved in some cognition, cognitive functions such as attention and language as well as emotion, emotional control such as regulating fear and pleasure responses, but its movement-related functions are the most solidly established. The human cerebellum does not initiate movement, but contributes to Motor coordination, coordination, precision, and accurate timing: it receives input from sensory systems of the spinal cord and from other parts of the brain, and integrates these inputs to fine-tune motor activity. Cerebellar damage produces disorders in Fine motor skill, fine movement, Equilibrioception, equilibrium, Human positions, posture, and motor learning in humans. Anatomica ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
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