Inactivation of the catalytic phosphatase domain of PTPRT/RPTPρ increases social interaction in mice.

Receptor protein tyrosine phosphatase rho (RPTPρ, gene symbol PTPRT) is a transmembrane protein expressed at high levels in the developing hippocampus, olfactory bulb, cortex, and cerebellum. It has an extracellular domain that interacts with other cell adhesion molecules, and it has two intracellular phosphatase domains, one of which is catalytically active. In a recent genome-wide association study, PTPRT was identified as a potential candidate gene for autism spectrum disorder (ASD) susceptibility.

Serial analysis of gene expression profiles of adult and aged mouse cerebellum.

Changes in specific cerebellar molecules contribute to impaired balance and motor coordination frequently observed in aged individuals. Serial analysis of gene expression (SAGE) was used to construct six libraries from adult and aged mouse cerebella. Combined unique tags for each group revealed 325 genes that were differentially expressed (p-chance View Article and Find Full Text PDF

Intracellular substrates of brain-enriched receptor protein tyrosine phosphatase rho (RPTPrho/PTPRT).

Receptor protein tyrosine phosphatase rho (RPTPrho/PTPRT) is a transmembrane protein that is highly expressed in the developing and adult central nervous system. It is a member of the RPTP R2B subfamily, which includes PTPkappa, PTPmu and PCP-2. Glutathione-S-transferase (GST) pulldown assays were used to show that RPTPrho interacts with several adherens junctional proteins in brain, including E-cadherin, N-cadherin, VE-cadherin (cadherin-5), desmoglein, alpha, beta and gamma catenin, p120(ctn) and alpha-actinin.

Digital transcriptome analysis in the aging cerebellum.

Serial analysis of gene expression (SAGE) was used to identify and quantify all expressed cerebellar genes in the adult (P92) and aged (P810) C57BL/6J mouse cerebellum. A "closest-neighbor" algorithm was used to differentiate low abundance tags from possible sequencing errors in both libraries. Unique tags were categorized into four groups: (1) novel genes; (2) ESTs; (3) RIKEN, KIA, and hypothetical genes; and (4) known genes.

Genomic structure and alternative splicing of murine R2B receptor protein tyrosine phosphatases (PTPkappa, mu, rho and PCP-2).

Background: Four genes designated as PTPRK (PTPkappa), PTPRL/U (PCP-2), PTPRM (PTPmu) and PTPRT (PTPrho) code for a subfamily (type R2B) of receptor protein tyrosine phosphatases (RPTPs) uniquely characterized by the presence of an N-terminal MAM domain. These transmembrane molecules have been implicated in homophilic cell adhesion. In the human, the PTPRK gene is located on chromosome 6, PTPRL/U on 1, PTPRM on 18 and PTPRT on 20.

Genomic organization and alternative splicing of the human and mouse RPTPrho genes.

Background: Receptor protein tyrosine phosphatase rho (RPTPrho, gene symbol PTPRT) is a member of the type IIB RPTP family. These transmembrane molecules have been linked to signal transduction, cell adhesion and neurite extension. The extracellular segment contains MAM, Ig-like and fibronectin type III domains, and the intracellular segment contains two phosphatase domains.

Tumorigenesis in transgenic mice in which the SV40 T antigen is driven by the brain-specific FGF1 promoter.

Gene expression can be manipulated by the introduction of a hybrid gene formed by linking a highly tissue-specific regulatory element to a gene whose expression might be expected to alter cellular function. Previously, we have shown that the human FGF1 gene contains four distinct tissue-specific promoters. In an effort to perturb the programming of proliferation and differentiation in a subset of neural cells, we have produced transgenic mice bearing the brain-specific promoter of the human FGF1 gene joined to the SV40 immediate early gene, which encodes the large T antigen.

Harmaline-induced changes in gamma aminobutyric acid(A) receptor subunit mRNA expression in murine olivocerebellar nuclei.

Increased CNS activity in the form of electrically or chemically induced seizures is known to alter the properties of GABA(A) receptors. The tremorgen, harmaline, causes a bursting pattern of activity in inferior olivary neurons, the effects of which are transmitted throughout the olivocerebellar circuit to other regions of the CNS. In situ hybridization was used to determine the effect of this increased activity on gamma aminobutyric acid(A) (GABA(A)) receptor subunit gene expression in the cerebellar Purkinje cell layer, deep cerebellar nuclei and inferior olivary complex of adult mice.

Modulation of GABA(A) receptor subunit mRNA levels in olivocerebellar neurons of purkinje cell degeneration and weaver mutant mice.

In olivocerebellar circuits, changes in the subunit composition of GABA(A) receptors occur at a time of extensive synaptic remodeling. In the deep cerebellar nuclei, GABA(A) receptor alpha1, beta2, and gamma2 subunit mRNA expression increases throughout neonatal development, whereas in the inferior olivary complex, the perinatal combination of alpha3, alpha5, beta3, and gamma2 mRNAs switches to the adult combination of alpha2, alpha4, beta3 and gamma1 during postnatal week 2. In situ hybridization was used to examine changes in subunit expression in the olivocerebellar nuclei of Purkinje cell degeneration and weaver mutant mice.

Identification and characterization of RPTP rho, a novel RPTP mu/kappa-like receptor protein tyrosine phosphatase whose expression is restricted to the central nervous system.

We describe the cloning, chromosomal localization and characterization of RPTPrho, a new member of the RPTPmu/kappa phosphatase subfamily. Receptor tyrosine phosphatases in this subfamily are comprised of a MAM domain near the N-terminal, an immunoglobulin-like domain, four fibronectin type III repeats, a single transmembrane domain, and a large juxtamembrane segment followed by two intracellular phosphatase domains. An alternatively spliced mini-exon was identified in the extracellular segment of RPTPrho, between the fourth fibronectin type III repeat and the transmembrane domain.

Novel receptor protein tyrosine phosphatase (RPTPrho) and acidic fibroblast growth factor (FGF-1) transcripts delineate a rostrocaudal boundary in the granule cell layer of the murine cerebellar cortex.

We have identified a novel receptor-like protein tyrosine phosphatase (RPTPrho) transcript whose expression in the cerebellar cortex is restricted to the granule cell layer of lobules 1-6. Acidic fibroblast growth factor (FGF-1) mRNA follows a similar cerebellar expression pattern. Together, the two markers define a sharp boundary in lobule 6, slightly caudal to the primary fissure.

Embryonic and postnatal expression of four gamma-aminobutyric acid transporter mRNAs in the mouse brain and leptomeninges.

The distribution of gamma-aminobutyric acid (GABA) transporter mRNAs (mGATs) was studied in mouse brain during embryonic and postnatal development using in situ hybridization with radiolabeled oligonucleotide probes. Mouse GATs 1 and 4 were present in the ventricular and subventricular zones of the lateral ventricle from gestational day 13. During postnatal development, mGAT1 mRNA was distributed diffusely throughout the brain and spinal cord, with the highest expression present in the olfactory bulbs, hippocampus, and cerebellar cortex.

Characterization of the 1B promoter of fibroblast growth factor 1 and its expression in the adult and developing mouse brain.

The present study elucidates the molecular structure of a murine fibroblast growth factor 1 (FGF-1) promoter and describes its distribution in the adult and developing mouse brain. A cDNA clone coding for FGF-1 was isolated from a mouse brain cDNA library. Nucleotide sequence analysis revealed that the clone contained, in addition to the protein coding region, an untranslated exon (FGF-1B) 34 base pairs upstream of the translation start codon ATG.

Light-microscopic distribution and parasagittal organisation of muscarinic receptors in rabbit cerebellar cortex.

Recent studies on the effects of intrafloccular injections of muscarinic agonists and antagonists on compensatory eye movements in rabbit, indicate that muscarinic receptors may play a modulatory role in the rabbit cerebellar circuitry. It was previously demonstrated by Neustadt et al. (1988), that muscarinic receptors in rabbit cerebellar cortex are distributed into alternating longitudinal zones of very high and very low receptor density.

Uncoupling of GABAA/benzodiazepine receptor alpha 1, beta 2, and gamma 2 subunit mRNA expression in cerebellar Purkinje cells of staggerer mutant mice.

The mammalian GABAA/benzodiazepine (GABAA/BZ) receptor is comprised of several subunit isoforms: alpha 1-6, beta 1-13, gamma 1-3 and delta. In the present studies, the expression of alpha 1, beta 2, and gamma 2 subunit mRNAs was examined in cerebellar Purkinje cells and deep cerebellar neurons of staggerer mutant mice during postnatal development. In control animals, the three subunit mRNAs were present at high density in Purkinje cells which, in adult animals, form a monolayer at the interface of the granule cell and molecular layers.

Differential expression of GABAA/benzodiazepine receptor subunit mRNAs and ligand binding sites in mouse cerebellar neurons following in vivo ethanol administration: an autoradiographic analysis.

The gamma-aminobutyric acidA (GABAA)/benzodiazepine (BZ) receptor is a pentamer composed of subunits belonging to several classes (alpha 1-6, beta 1-4, gamma 1-4, delta, and rho 1 and rho 2). In situ hybridization, radioligand autoradiography, and immunocytochemistry were used to examine GABAA/BZ receptor alpha 1, alpha 6, beta 2, beta 3, and gamma 2 subunit expression in murine Purkinje, granule, and deep cerebellar neurons after in vivo ethanol exposure. Chronic ethanol treatment resulted in decreased alpha 1 subunit mRNA expression in each cell type, whereas the expression of alpha 6 and gamma 2 subunit mRNA levels increased; no changes were observed in the expression of beta 2 and beta 3 subunit mRNA.

Developmental changes in the expression of gamma-aminobutyric acidA/benzodiazepine receptor subunit mRNAs in the murine inferior olivary complex.

The pharmacological and physiological properties of ligand-gated ion channels are dependent on their subunit composition; spontaneously occurring changes in subunit composition during neuronal development may result in dramatic functional differences between embryonic and adult forms of the receptor complex. In the present study, in situ hybridization with antisense cRNA probes was used to examine the subunit composition of the gamma-aminobutyric acidA/benzodiazepine (GABAA/BZ) receptor in the developing inferior olivary complex. This receptor is thought to be a pentameric chloride channel comprised of selected alpha, beta, gamma, delta, and rho subunits, the majority of which have several isoforms: alpha 1-6, beta 1-4, gamma 1-4, and rho 1,2.

GABAA/benzodiazepine receptor alpha 6 subunit mRNA in granule cells of the cerebellar cortex and cochlear nuclei: expression in developing and mutant mice.

The gamma aminobutyric acidA/benzodiazepine (GABAA/BZ) receptor is a multisubunit (alpha, beta, gamma, delta, and rho) ligand-gated chloride channel; there are several variants of the alpha, beta, and gamma subunits, each of which has been localized throughout the central nervous system. A large number of GABAA/BZ subunit variants are expressed within the cerebellar cortex. In previous studies from other laboratories, alpha 6 subunit mRNA has been reported to be present exclusively in cerebellar granule cells.

GABAA/benzodiazepine receptor gamma 2 subunit gene expression in developing normal and mutant mouse cerebellum.

Recent studies have identified several subunits (alpha, beta, gamma and delta) of the gamma-aminobutyric acidA/benzodiazepine receptor; each consists of several variants. The gamma 2 subunit appears to mediate the interaction of the alpha and beta subunits making the receptor capable of modulation by benzodiazepines. In the present studies, the expression of mRNA encoding the gamma 2 subunit was examined in the cerebellum during development and in adult Purkinje cell degeneration, lurcher and reeler mutant mice.

Differential expression of GABAA/benzodiazepine receptor beta 1, beta 2, and beta 3 subunit mRNAs in the developing mouse cerebellum.

Gamma aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the mammalian cerebellum. Cerebellar granule, Purkinje, and deep nuclear neurons are known to receive GABAergic afferents. Since GABA exerts its inhibitory effects via GABA receptors, it is of interest to determine the temporal relationship between the formation of GABAergic synapses and the expression of genes coding for the GABA receptor.

Ontogeny of GABAA/benzodiazepine receptor subunit mRNAs in the murine inferior olive: transient appearance of beta 3 subunit mRNA and [3H]muscimol binding sites.

The GABAA/benzodiazepine receptor consists of at least four subunits, alpha, beta, gamma and delta, each comprised of several variants. The developmental expression of the alpha 1, beta 1-3, gamma 2 and delta subunits was studied in the murine inferior olivary nucleus by in situ hybridization with antisense cRNA probes. The postnatal appearance and distribution of [3H]flunitrazepam and [3H]muscimol binding sites, alpha and beta subunit-specific ligands respectively, were also studied autoradiographically.

Stability of GABAA/benzodiazepine receptor alpha 1 subunit mRNA expression in reeler mouse cerebellar Purkinje cells during postnatal development.

A [35S]cRNA probe was used for the visualization of GABAA/benzodiazepine (GABAA/BZ) receptor alpha 1 subunit mRNA in developing reeler mutant mouse cerebellum. A clear hybridization signal was observed throughout the malformed reeler cerebellum from birth. Labeling was associated with Purkinje cell bodies located in three subcortical masses.

Expression of GABAA/benzodiazepine receptor alpha 1-subunit mRNA and [3H]flunitrazepam binding sites during postnatal development of the mouse cerebellum.

Previous studies have shown that the alpha subunit of the GABAA receptor contains the flunitrazepam binding site. In the present study, in situ hybridization and receptor autoradiography were used to examine the temporal and spatial relationships between alpha 1 subunit mRNA and [3H]flunitrazepam binding sites in the developing mouse cerebellum. A [35S]cRNA probe was used to study the expression of GABAA/benzodiazepine receptor alpha 1 subunit mRNA by in situ hybridization.

Distribution of muscarinic receptors in the developing rodent cerebellum.

The distribution of muscarinic receptors in the developing rodent cerebellum was studied by light microscopic autoradiography of [3H]quinuclidinyl benzilate binding sites. Muscarinic receptors were not detected in the mouse cerebellar plate until embryonic day 16, at which time they were clustered in the ventromedial region of the cerebellar anlagen. At postnatal day 1, additional areas of higher grain density became visible in the dorsolateral medullary zone, internal to the newly forming granular layer.