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A Dautigny

Publications and source records attributed to A Dautigny.

At least 37 records · Page 2Linked to original sources
PubMed1994

Characterization and expression of the cDNA coding for the human myelin/oligodendrocyte glycoprotein.

We report here the characterization of a full-length cDNA encoding the human myelin/oligodendrocyte glycoprotein (MOG). The sequence of the coding region of the human MOG cDNA is highly homologous to that of other previously cloned mouse, rat, and bovine MOG cDNAs, but the 3' untranslated region differs by an insertion of an Alu sequence between nucleotides 1,590 and 1,924. Accordingly, northern blot analyzes with cDNA probes corresponding to the coding region or the 3' untranslated Alu-containing sequence revealed a single band of 2 kb, rather than the 1.6 kb of bovine, rat, or mouse MOG cDNA(s). Immunocytochemical analysis of HeLa cells transfected with human MOG cDNA, which was performed using a specific antibody raised against whole MOG, clearly indicated that MOG is expressed at the cell surface as an intrinsic protein. These data are in accordance with the predicted amino acid sequence, which contains a signal peptide and two putative transmembrane domains. The knowledge of the human MOG sequence should facilitate further investigations on its potential as a target antigen in autoimmune demyelinating diseases like multiple sclerosis.

Amino Acid Sequence↗
PubMed1994

Genetic homogeneity of Pelizaeus-Merzbacher disease: tight linkage to the proteolipoprotein locus in 16 affected families. PMD Clinical Group.

Among the numerous leukodystrophies that have an early onset and no biochemical markers, Pelizaeus-Merzbacher disease (PMD) is one that can be identified using strict clinical criteria and demonstrating an abnormal formation of myelin that is restricted to the CNS in electrophysiological studies and brain magnetic resonance imaging (MRI). In PMD, 12 different base substitutions and one total deletion of the genomic region containing the PLP gene have been reported, but, despite extensive analysis, PLP exon mutations have been found in only 10%-25% of the families analyzed. To test the genetic homogeneity of this disease, we have carried out linkage analysis with polymorphic markers of the PLP genomic region in 16 families selected on strict diagnostic criteria of PMD. We observed a tight linkage of the PMD locus with markers of the PLP gene (cDNA PLP, exon IV polymorphism) and of the Xq22 region (DXS17, DXS94, and DXS287), whereas the markers located more proximally (DXYS1X and DXS3) or distally (DXS11) were not linked to the PMD locus. Multipoint analysis gave a maximal location score for the PMD locus (13.98) and the PLP gene (8.32) in the same interval between DXS94 and DXS287, suggesting that in all families PMD is linked to the PLP locus. Mutations of the extraexonic PLP gene sequences or of another unknown close gene could be involved in PMD. In an attempt to identify molecular defects of this genomic region that are responsible for PMD, these results meant that RFLP analysis could be used to improve genetic counseling for the numerous affected families in which a PLP exon mutation could not be demonstrated.

Adolescent↗
PubMed1993

Myelin/oligodendrocyte glycoprotein is a member of a subset of the immunoglobulin superfamily encoded within the major histocompatibility complex.

Myelin/oligodendrocyte glycoprotein (MOG) is found on the surface of myelinating oligodendrocytes and external lamellae of myelin sheaths in the central nervous system, and it is a target antigen in experimental autoimmune encephalomyelitis and multiple sclerosis. We have isolated bovine, mouse, and rat MOG cDNA clones and shown that the developmental pattern of MOG expression in the rat central nervous system coincides with the late stages of myelination. The amino-terminal, extracellular domain of MOG has characteristics of an immunoglobulin variable domain and is 46% and 41% identical with the amino terminus of bovine butyrophilin (expressed in the lactating mammary gland) and B-G antigens of the chicken major histocompatibility complex (MHC), respectively; these proteins thus form a subset of the immunoglobulin superfamily. The homology between MOG and B-G extends beyond their structure and genetic mapping to their ability to induce strong antibody responses and has implications for the role of MOG in pathological, autoimmune conditions. We colocalized the MOG and BT genes to the human MHC on chromosome 6p21.3-p22. The mouse MOG gene was mapped to the homologous band C of chromosome 17, within the M region of the mouse MHC.

Aging↗
PubMed1993

The major peripheral myelin protein zero gene: structure and localization in the cluster of Fc gamma receptor genes on human chromosome 1q21.3-q23.

We have characterized the human gene encoding the major peripheral myelin protein zero (P0) and assigned it, by in situ hybridization, to the q21.3-q23 region of human chromosome 1. This region is known to contain a cluster of interspersed genes coding for the related human leukocyte receptors of the Fc portion of the immunoglobulin G (Fc gamma RI, II, III). This colocalization was refined by the finding of a yeast artificial chromosome (YAC) of the Centre d'Etude du Polymorphisme Humain (CEPH) library, hybridizing to the P0 and Fc gamma RIIA genes, demonstrating their physical linkage. These data may have important implications in demyelinating diseases studies like Charcot-Marie-Tooth disease type 1B (CMT1B).

Amino Acid Sequence↗
PubMed1993

Pelizaeus-Merzbacher disease: a frameshift deletion/insertion event in the myelin proteolipid gene.

Among the central nervous system (CNS) dysmyelinating disorders, Pelizaeus-Merzbacher disease (PMD) has been individualized by its X-linked mode of inheritance and the existence of corresponding animal models. Mutations in the major myelin proteolipid (PLP) gene coding for PLP and its splicing variant DM20 protein, have been demonstrated in animal mutants and more recently in PMD affected patients. We have identified, in a two-generation PMD affected family, an insertion/deletion event in the exon IV of the PLP gene, leading to the synthesis of predicted truncated PLP and DM20 proteins with altered carboxyl terminal end. This is the first report of a frameshift mutation in the PLP gene in PMD.

Amino Acid Sequence↗
PubMed1991

Pelizaeus-Merzbacher disease: a valine to phenylalanine point mutation in a putative extracellular loop of myelin proteolipid.

In the central nervous system, myelin proteolipid protein isoforms (PLP and DM20) play an essential structural role in myelination. It has been shown in several species that myelination is impaired by molecular defects resulting from single base mutations in the PLP gene. We have used DNA amplification by polymerase chain reaction to study the PLP gene coding regions from 17 patients in 15 unrelated families with similar Pelizaeus-Merzbacher phenotype. In one case amplification of peripheral nerve PLP/DM20 cDNAs revealed that a silent T----C transition was unrelated to the disease. In one family a nonsilent mutation was identified that leads to a phenylalanine substitution for valine-218 in PLP/DM20 proteins. We investigated the inheritance of the mutant allele in 19 subjects of this four-generation family and found a strict cosegregation of the Phe218 substitution with transmission and expression of the disease. The effect of the Val218----Phe mutation is discussed in the frame of a recently suggested topological model of PLP/DM20, according to which Val218 is part of an extracellular loop that connects the last two of four membrane-spanning alpha-helices.

Animals↗
PubMed1991

Major Myelin proteolipid: the 4-alpha-helix topology.

Several conflicting models have been proposed for the membrane arrangement of the major myelin proteolipid (PLP). We have compared features of the sequence of PLP with those of other eukaryotic integral membrane proteins, with the view of identifying the most likely transmembrane topology. A new, simple model is suggested, which features four hydrophobic alpha-helices spanning the whole thickness of the lipid bilayer. Its orientation may be such that both the N- and C-termini face the cytosol. None of the biochemical, biophysical or immunological experiments hitherto reported provides incontrovertible evidence against the model. The effect or absence thereof of various PLP mutations is discussed in the frame of the proposed 4-helix topology.

Amino Acid Sequence↗
PubMed1991

cDNA and amino acid sequences of rainbow trout (Oncorhynchus mykiss) lysozymes and their implications for the evolution of lysozyme and lactalbumin.

The complete 129-amino-acid sequences of two rainbow trout lysozymes (I and II) isolated from kidney were established using protein chemistry microtechniques. The two sequences differ only at position 86, I having aspartic acid and II having alanine. A cDNA clone coding for rainbow trout lysozyme was isolated from a cDNA library made from liver mRNA. Sequencing of the cloned cDNA insert, which was 1 kb in length, revealed a 432-bp open reading frame encoding an amino-terminal peptide of 15 amino acids and a mature enzyme of 129 amino acids identical in sequence to II. Forms I and II from kidney and liver were also analyzed using enzymatic amplification via PCR and direct sequencing; both organs contain mRNA encoding the two lysozymes. Evolutionary trees relating DNA sequences coding for lysozymes c and alpha-lactalbumins provide evidence that the gene duplication giving rise to conventional vertebrate lysozymes c and to lactalbumin preceded the divergence of fishes and tetrapods about 400 Myr ago. Evolutionary analysis also suggests that amino acid replacements may have accumulated more slowly on the lineage leading to fish lysozyme than on those leading to mammal and bird lysozymes.

Amino Acid Sequence↗
PubMed1991

Developmental regulation of calmodulin gene expression in rat brain and skeletal muscle.

Three different calmodulin genes that encode the identical protein have been identified in the rat (Nojima, 1989); however, calmodulin gene expression at the various stages of tissue differentiation and maturation has not been previously determined. We have quantitated the content of mRNAs encoding calmodulin in the developing brain and skeletal muscle using RNA blot analysis with three specific cDNA probes. Our results show that five species of calmodulin mRNAs: 4.0 and 1.7 kb for CaM I, 1.4 kb for CaM II, and 2.3 and 0.8 kb for CaM III are detectable at all ages in the brain as well as in skeletal muscle but exhibit a tissue-specific developmental pattern of expression. The comparison of the temporal pattern of calmodulin gene expression with both mitotic activity, as demonstrated by cyclin A mRNA levels, and differentiation and maturation of specific brain or muscle regions is consistent with calmodulin involvement in development.

Animals↗
PubMed1991

Proteolipid DM-20 predominates over PLP in peripheral nervous system.

The major central nervous system (CNS) myelin proteolipid (PLP) is also expressed in the peripheral nervous system (PNS). This paper gives evidence that DM-20, an isoform of PLP, also occurs in rat sciatic nerves, where, in contrast to what is seen in CNS myelin, it predominates over PLP. This conclusion was reached on the basis of results obtained by immunoblot analysis of a crude proteolipid extract from adult peripheral nerve with two site-specific anti-proteolipid (PLP and DM-20) antibodies. This finding was further corroborated by characterization of the products obtained by Polymerase Chain Reaction (PCR) amplification of cDNAs synthesized from total RNA of 14-day-old sciatic nerves. The significance of the occurrence of these proteolipids in PNS remains obscure.

Amino Acid Sequence↗
PubMed1991

In situ localization of NF-H neurofilament subunit mRNAs in rat brain.

The expression of NF-H neurofilament subunit mRNAs was investigated in the rat brain at different ontogenic stages. The levels of NF-H mRNAs vary 15-fold among brain regions with the highest level in the brainstem. In situ localization studies revealed that the NF-H mRNAs are mainly concentrated in the brainstem motoneuron nuclei. By increasing the sensitivity of the hybridization method, NF-H mRNAs could also be localized in neurons present in the cortex, thalamus and hippocampus areas. Minor amounts of NF-H mRNAs were already detected at 17-day embryonic stages.

Animals↗
PubMed1989

Developmental expression of myelin proteolipid, basic protein, and 2',3'-cyclic nucleotide 3'-phosphodiesterase transcripts in different rat brain regions.

RNA was extracted from five different rat brain regions during development, starting from embryonic day 15 (E15) until postnatal day 60 (P60). These RNA preparations were analyzed by both Northern and dot blot for their content of 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNPase), myelin proteolipid protein (PLP), and myelin basic protein (MBP) -specific transcripts. CNPase mRNA was readily detectable at E15 and PLP mRNA at P1 in all brain regions examined. In contrast, expression of MBP mRNA followed a caudorostral gradient. It was first observed at P1 in the mesencephalon and at P9-P11 in the olfactory bulb. Expression of these three transcripts displayed two types of developmental profiles. One was termed biphasic because the specific mRNA level increased regularly and then reached a plateau level. The other developmental profile was termed triphasic, because there was a gradual increase in the level of specific transcripts with a sudden appearance of a sharp peak followed by a decline to a plateau level. When the triphasic pattern was observed, the date of the peak appearance was probe-, but not region-, dependent. It was P15 for CNPase, P18 for MBP, and P21 for PLP. As these peaks occurred at a time during development when myelination was the most active, we postulate the existence of a transient external signal, perhaps neuronal, which would be responsible for this increased amount of myelin-related transcripts.

2',3'-Cyclic-Nucleotide Phosphodiesterases↗
PubMed1988

The large neurofilament subunit (NF-H) of the rat: cDNA cloning and in situ detection.

A lambda gt11 expression library was screened with a polyclonal antiserum directed against Wla Wolfgram protein which corresponds to the 2',3'-cyclic nucleotide 3'-phosphohydrolase. This antiserum also recognizes epitopes of the high protein subunit of neurofilaments (NF-H). An NF-H cDNA clone (pNF-H1: 1.7 kb) was isolated and characterized. Using pNF-H1 as a probe, a second cDNA clone (pNF-H2: 3 kb) was isolated from the lambda gt11 library. The two clones were sequenced and pNF-H2 was found to encode 80% of rat NF-H protein (coil-2 and C-terminal region). The C-terminal region contains an unusual sequence with stretches of repeats of Lys-Ser-Pro which represent possible phosphorylation sites. Specific localization in neurons of the corresponding mRNA was demonstrated by in situ hybridization using the pNF-H1 as a probe.

Amino Acid Sequence↗
PubMed1988

The gene encoding the large human neurofilament subunit (NF-H) maps to the q121-q131 region on human chromosome 22.

Using a rat cDNA probe encoding for the C-terminal extension of the large neurofilament subunit (NF-H), we have assigned, by in situ hybridization, the human NF-H gene to the q121-q131 region of chromosome 22. This localization may have implications in neurological diseases such as meningioma where a recessive locus involved in oncogenesis is located within this region.

Animals↗
PubMed1986

Myelin proteolipid protein (PLP and DM-20) transcripts are deleted in jimpy mutant mice.

The myelin-associated proteolipid protein, PLP, is one of the two major components of the central nervous system (CNS) myelin. We analyze, by using a rat PLP cDNA and S1 nuclease protection experiments, the PLP transcripts in the mouse brain and show that the PLP gene encodes two different but related mRNA transcripts, the PLP and the DM-20 transcripts. On the other hand, we demonstrate that in the jimpy mutant, which is characterized by an abnormal CNS myelination, both these transcripts are partially deleted in the 3' end of their coding region. The deletion is 70 (+/- 5) nucleotides long. Implications of this finding for the synthesis of PLP and DM-20 proteins in the mutant are discussed.

Animals↗
PubMed1985

Molecular cloning and nucleotide sequence of a cDNA clone coding for rat brain myelin proteolipid.

A cDNA library from rat brain was constructed in pBR322 and screened with a 14-mer mixed oligonucleotide probe based on residues 231-235 of bovine proteolipid (PLP). A positive clone was isolated: it contained a 1334-base-pair cDNA insert and was subjected to DNA sequence analysis. The cDNA encoded information for the 276 amino acids of rat PLP. Comparison with bovine PLP sequence showed a complete amino acid sequence homology except for 4 amino acid residues.

Animals↗