Myotonic dystrophy (DM) is commonly associated with CTG repeat expansions within the gene for DM-protein kinase (DMPK). The effect of altered expression levels of DMPK, which is ubiquitously expressed in all muscle cell lineages during development, was examined by disrupting the endogenous Dmpk gene and overexpressing a normal human DMPK transgene in mice. Nullizygous (-/-) mice showed only inconsistent and minor size changes in head and neck muscle fibres at older age, animals with the highest DMPK transgene expression showed hypertrophic cardiomyopathy and enhanced neonatal mortality. However, both models lack other frequent DM symptoms including the fibre-type dependent atrophy, myotonia, cataract and male-infertility. These results strengthen the contention that simple loss- or gain-of-expression of DMPK is not the only crucial requirement for development of the disease.
To identify possible ligands of the orphan somatostatin-like receptor 1 (SLC-1), rat brain extracts were analyzed by using the functional expression system of Xenopus oocytes injected with cRNAs encoding SLC-1 and G protein-gated inwardly rectifying potassium channels (GIRK). A strong inward current was observed with crude rat brain extracts which upon further purification by cation exchange chromatography and high performance liquid chromatography (HPLC) yielded two peptides with a high agonist activity. Mass spectrometry and partial peptide sequencing revealed that one peptide is identical with the neuropeptide melanin concentrating hormone (MCH), the other represents a truncated version of MCH lacking the three N-terminal amino acid residues. Xenopus oocytes expressing the MCH receptor responded to nM concentrations of synthetic MCH not only by the activation of GIRK-mediated currents but also by the induction of Ca 2 dependent chloride currents mediated by phospholipase C. This indicates that the MCH receptor can couple either to the G i -or G q -mediated signal transduction pathway, suggesting that MCH may serve for a number of distinct brain functions including food uptake behavior.z 1999 Federation of European Biochemical Societies.
By using the yeast two-hybrid system we identified a novel protein from the human brain interacting with the C terminus of somatostatin receptor subtype 2. This protein termed somatostatin receptor interacting protein is characterized by a novel domain structure, consisting of six N-terminal ankyrin repeats followed by SH3 and PDZ domains, several proline-rich regions, and a C-terminal sterile ␣ motif. It consists of 2185 amino acid residues encoded by a 9-kilobase pair mRNA; several splice variants have been detected in human and rat cDNA libraries. Sequence comparison suggests that the novel multidomain protein, together with cortactinbinding protein, forms a family of cytoskeletal anchoring proteins. Fractionation of rat brain membranes indicated that somatostatin receptor interacting protein is enriched in the postsynaptic density fraction. The interaction of somatostatin receptor subtype 2 with its interacting protein was verified by overlay assays and coimmunoprecipitation experiments from transfected human embryonic kidney cells. Somatostatin receptor subtype 2 and the interacting protein display a striking overlap of their expression patterns in the rat brain. Interestingly, in the hippocampus the mRNA for somatostatin receptor interacting protein was not confined to the cell bodies but was also observed in the molecular layer, suggesting a dendritic localization of this mRNA.Targeting of neurotransmitter receptors to postsynaptic or presynaptic sites is an area that has been widely studied in recent years; a large body of evidence has accumulated showing that many receptors are anchored at their specifc site of action by specialized anchoring proteins, which may link receptors to components of the synaptic structure or the cytoskeleton (1, 2). This is true for inhibitory as well as excitatory receptors of the family of ligand-gated ion channels. For the second large family of neurotransmitter receptors, the seven transmembrane domain G-protein-coupled receptors, only very recently have some proteins been identified that may be involved in anchoring or linkage to the cytoskeleton. These include the homer proteins, which are tightly associated with metabotropic glutamate receptors via a PDZ 1 domain in homer and the C terminus of the mGluRs (3). However, for the large majority of G-protein-coupled receptors, no intracellular associated proteins have been identified so far beyond those proteins which are necessary for signal transduction and functional regulation of the receptors, i.e. the G-proteins and proteins of the arrestin family (4).We have begun to address this issue for members of the somatostatin receptor family (SSTRs). SSTRs are widely expressed in neuronal tissue and modulate synaptic responses by interacting with inhibitory G-proteins in presynaptic as well as postsynaptic compartments of neurons (e.g. Refs. 5-8). Recently we have used the yeast two-hybrid system to screen for proteins intracellularly associated with SSTR2, one of the major SSTR subtypes in the mammalian brain. Here we show t...
In order to elucidate the cellular and molecular processes which are involved in Norrie disease (ND), we have used gene targeting technology to generate ND mutant mice. The murine homologue of the ND gene was cloned and shown to encode a polypeptide that shares 94% of the amino acid sequence with its human counterpart. RNA in situ hybridization revealed expression in retina, brain and the olfactory bulb and epithelium of 2 week old mice. Hemizygous mice carrying a replacement mutation in exon 2 of the ND gene developed retrolental structures in the vitreous body and showed an overall disorganization of the retinal ganglion cell layer. The outer plexiform layer disappears occasionally, resulting in a juxtaposed inner and outer nuclear layer. At the same regions, the outer segments of the photoreceptor cell layer are no longer present. These ocular findings are consistent with observations in ND patients and the generated mouse line provides a faithful model for study of early pathogenic events in this severe X-linked recessive neurological disorder.
A search for genes with sequence homologies to the FMR1 gene resulted in the isolation of mouse and human homologues of the recently described FXR1 gene. The mouse FXR1 gene shares amino acid identity and similarity of 99.1% and 99.6%, respectively, with the human FXR1 gene and amino acid identify and similarity of 67.3% and 79.5% respectively, with the mouse FMR1 gene. The 3' untranslated region of the FXR1 gene is extremely conserved between human and mouse. The gene structure of FXR1 is very similar to that of FMR1 and both genes probably originate from a common ancestral gene. In contrast to the previously published localization, we mapped the transcribed gene to chromosome region 3q28. An intronless form of the FXR1 gene, either processed functional homologue or pseudogene was localized to 12q12. Northern blot analysis of the human FXR1 gene revealed an expression pattern of a housekeeping gene with stronger expression in muscle. RNA in situ hybridization to sections of mouse embryo and adult tissues has shown that during embryonic development the mouse FXR1 mRNA is expressed in different tissues, most prominent in skeletal muscle, the gonads and distinct regions of the central nervous system, and that the expression is restricted to proliferating cells. While FMR1 is highly expressed in proliferating spermatogonia, FXR1 is highly expressed in postmeiotic spermatids.
The protein tyrosine phosphatases PTP-SL and PTPBR7 differ only in the length of their N-terminal domain. We show here that PTP-SL and PTPBR7 are isoforms derived from a single gene (Ptprr) through developmentally regulated use of alternative promoters. Isoform-specific reverse transcriptase-polymer chain reaction (RT-PCR) and RNA in situ hybridization experiments reveal that PTPBR7 is expressed during early embryogenesis in spinal ganglia cells as well as in developing Purkinje cells. Post-natally, PTPBR7 is expressed in various regions of the adult mouse brain, but expression in Purkinje cells has ceased and is replaced by the PTP-SL-specific transcript. In transient transfection experiments it is confirmed that PTPBR7 is a type I transmembrane protein tyrosine phosphatase (PTPase). PTP-SL, however, appears to be a cytosolic membrane-associated PTPase that is located at perinuclear vesicular structures that partly belong to the endosomal compartment. Thus, during maturation of Purkinje cells, a gene-promoter switch results in the replacement of a receptor-type PTPase by a cytosolic vesicle-associated isoform.
The murine homologue of the human motility-stimulating protein autotaxin (ATX) was identified as a BMP2 upregulated gene by subtractive cloning from mesenchymal progenitors C3H10T1/2 (Bächner, D., Ahrens, M., Betat, N., Schröder, D., Hoffmann. A., Lauber, J., Steinert, P., Flohe, L., Gross, G., 1998. Bmp-2 downstream targets in mesenchymal development identified by subtractive cloning from recombinant mesenchymal progenitors (C3H10T1/2). Dev. Dyn. 213, 398-411). ATX mRNA transcription is induced during BMP2 mediated osteo-/chondrogenic differentiation in vitro several orders of magnitude. To delineate a potential role for ATX in osteo-/chondrogenic development, its expression pattern during murine embryogenesis was examined in comparison with Col1a1 and Col2a1, a marker either of osteoblast, odontoblast and tendon or of chondrocyte development, respectively. Localization of murine ATX was first observed in the floor plate of the neural tube at day 9.5 of mouse embryonic development. Later, enhanced ATX expression levels were observed in proliferating subepithelial mesenchyme, during osteo-/chondrogenic and tooth development, in choroid plexus epithelium, in late kidney development, and in smooth muscles of the ductus deferens and the bladder.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
334 Leonard St
Brooklyn, NY 11211
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.