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D J Gilbert

Publications and source records attributed to D J Gilbert.

At least 235 records · Page 13Linked to original sources
PubMed1995

Growth/differentiation factor-10: a new member of the transforming growth factor-beta superfamily related to bone morphogenetic protein-3.

We have identified a new member of the transforming growth factor-beta (TGF-beta) superfamily, growth/differentiation factor-10 (GDF-10), which is highly related to bone morphogenetic protein-3 (BMP-3). The nucleotide sequence of GDF-10 encodes a predicted protein of 476 amino acids with a molecular weight of approximately 52,000. The GDF-10 polypeptide contains a potential signal sequence for secretion, a putative RXXR proteolytic processing site, and a carboxy-terminal domain with considerable homology to other known members of the TGF-beta superfamily. In the mature carboxy-terminal domain GDF-10 is more homologous to BMP-3 (83% amino acid sequence identity) than to any other previously identified TGF-beta family member. GDF-10 also shows significant homology to BMP-3 (approximately 30% amino acid sequence identity) in the pro- region of the molecule. Based on these sequence comparisons, GDF-10 and BMP-3 define a new subgroup within the larger TGF-beta superfamily. By Northern analysis, GDF-10 mRNA was detected primarily in murine uterus, adipose tissue, and brain and to a lesser extent in liver and spleen. In addition, GDF-10 mRNA was present in both neonatal and adult bone samples, with higher levels being detected in calvaria than in long bone. These results suggest that GDF10 may play multiple roles in regulating cell differentiation events, including those involved in skeletal morphogenesis. Gdf10 was mapped to the proximal region of mouse chromosome 14 close to a region known to contain a spontaneous recessive mutation that is associated with a craniofacial defect.

Amino Acid Sequence↗
PubMed1995

Studies of cloning, chromosomal mapping, and embryonic expression of the mouse Rab geranylgeranyl transferase beta subunit.

The mouse Rab geranylgeranyl transferase beta subunit has been cloned from a mouse E8.5 embryonic cDNA library. Sequence comparison reveals 97.4% sequence identity at the amino acid level to the rat clone isolated from an adult rat brain cDNA library. This gene, given a gene symbol of Rabggtb, is mapped in the distal region of mouse chromosome 3. It is ubiquitously expressed in adult animals but displays an interesting pattern of expression during a specific time of embryonic development. The expression of this gene can be detected in the whole embryos during early embryonic stages and is specifically concentrated in the developing brain, heart, and liver between gestation stages of E11.5 and E13.5. In addition, the expression of this gene is induced by retinoic acid in a mouse embryonal carcinoma cell line, P19.

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PubMed1995

Identification of mammalian noggin and its expression in the adult nervous system.

The multiple roles of noggin during dorsal fate specification in Xenopus embryos, together with noggin's ability to directly induce neural tissue, inspired an effort to determine whether a similar molecule exists in mammals. Here we describe the identification of human and rat noggin and explore their expression patterns; we also localize the human NOGGIN gene to chromosome 17q22, and the mouse gene to a syntenic region of chromosome 11. Mammalian noggin is remarkably similar in its sequence to Xenopus noggin, and is similarly active in induction assays performed on Xenopus embryo tissues. In the adult mammal, noggin is most notably expressed in particular regions of the nervous system, such as the tufted cells of the olfactory bulb, the piriform cortex of the brain, and the Purkinje cells of the cerebellum, suggesting that one of the earliest acting neural inducers also has important roles in the adult nervous system.

Amino Acid Sequence↗
PubMed1994

Mouse A-myb encodes a trans-activator and is expressed in mitotically active cells of the developing central nervous system, adult testis and B lymphocytes.

C-myb encodes a transcriptional activator that is essential for the development of the hematopoietic system but appears to lack major roles in non-hematopoietic cells. The identification of two conserved myb-related genes, designated A-myb and B-myb, has raised the possibility that these genes are functional equivalents of c-myb in non-hematopoietic cells. Here, we report the isolation and preliminary characterization of the mouse A-myb gene. Mouse A-myb maps to the proximal region of chromosome 1 and encodes a transcriptional activator with properties similar to those of the c-myb and v-myb proteins. During embryo-genesis A-myb is predominantly expressed in several regions of the developing central nervous system (CNS) and the urogenital ridge. Expression in the CNS is confined to the neural tube, the hindbrain, the neural retina and the olfactory epithelium, and coincides with the presence of proliferating immature neuronal precursor cells. In the adult mouse, A-myb is expressed during the early stages of sperm cell differentiation and in B lymphocytes located in germinal centers of the spleen. Taken together, these results suggest a role for A-myb in the proliferation and/or differentiation of neurogenic, spermatogenic and B-lymphoid cells.

Amino Acid Sequence↗
PubMed1994

The genes encoding the glutamate receptor subunits KA1 and KA2 (GRIK4 and GRIK5) are located on separate chromosomes in human, mouse, and rat.

The chromosomal localization of the human and rat genes encoding the kainate-preferring glutamate receptor subunits KA1 and KA2 (GRIK4 and GRIK5, respectively) was determined by Southern analysis of rat x mouse and human x mouse somatic cell hybrid panels and by fluorescence in situ hybridization. The localization of the mouse genes (Grik4 and Grik5) was established by interspecific backcross mapping. GRIK4 and GRIK5 are located on separate chromosomes (Chrs) in all species. GRIK4 mapped to human Chr 11q22.3, mouse Chr 9, and rat Chr 8. GRIK5 mapped to human Chr 19q13.2, mouse Chr 7, and rat Chr 1. The genes encoding the (R,S)-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA)-preferring subunit GluR4, or GluRD (GRIA4), the neural cell adhesion molecule (NCAM), the D2 dopamine receptor (DRD2), and the Thy-1 cell surface antigen (THY1) have all been previously mapped to the human Chr 11q22 region. The mapping of the human GRIK4 and GRIK5 genes confirms and extends the relationship between human Chr 11 and mouse Chr 9 and also human Chr 19 and mouse Chr 7. GRIK4 is the fifth gene shared by human Chr 11 and rat Chr 8, whereas GRIK5 is 1 out of the 12 genes that are located on both human Chr 19 and rat Chr 1. Our data extend the conserved synteny established between certain human, mouse, and rat Chrs.

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PubMed1994

Mouse excitatory amino acid transporter EAAT2: isolation, characterization, and proximity to neuroexcitability loci on mouse chromosome 2.

Glutamate and aspartate are excitatory neurotransmitters that have been implicated in a number of pathological states of the nervous system. Accumulation of extracellular excitatory amino acids can be cytotoxic and may also lower the seizure threshold in epilepsy. An important function of the Na(+)-dependent high-affinity excitatory amino acid transporter (EAAT) is the reuptake of secreted amino acid neurotransmitter, possibly maintaining extracellular amino acid concentrations at nontoxic and nonepileptogenic levels. We have isolated the mouse cDNA for EAAT2, a neurotransmitter transporter that shares extensive amino acid sequence homology with one of several previously cloned high-affinity glutamate transporters. The mouse EAAT2 amino acid sequence shares 99 and 97% identity with its rat and human homologues, respectively. It is expressed predominantly in the brain, where it may function as a glia-specific transporter. In an interspecific backcross analysis Eaat2 maps to the central region of mouse chromosome 2, where it is located near quantitative trait loci that modulate neuroexcitability and seizure frequency in mouse models of alcohol withdrawal and epilepsy.

Amino Acid Sequence↗
PubMed1994

Characterization and mapping of the Rapsn gene encoding the 43-kDa acetylcholine receptor-associated protein.

We have cloned and characterized mouse genomic DNA containing the gene for the 43-kDa acetylcholine receptor-associated protein. The gene extends over 12 kb and consists of 8 exons. RNase protection and sequence analysis have been used to define the intron/exon boundaries including 174 and 214 bp of 5' and 3' untranslated sequence in exons 1 and 8, respectively. Interestingly, the exon/intron organization is consistent with structural domains predicted from amino acid sequence conservation among 3 species of 43K. Finally, the 43K locus, designated Rapsn, has been mapped to the central region of mouse chromosome 2.

Amino Acid Sequence↗
PubMed1994

Genomic organization and chromosomal localization of mouse Eplg2, a gene encoding a binding protein for the receptor tyrosine kinase elk.

The human gene EPLG2 (Eph ligand-2) encodes a potential ligand for the receptor tyrosine kinase elk. High sequence conservation between the human and the rat cDNAs and developmentally regulated expression of the rat gene suggest that the protein encoded by EPLG2 plays an important role in mammalian development. To facilitate analysis of the physiological role of the protein, we have cloned and characterized a 24-kb region of mouse genomic DNA containing the mouse homologue of EPLG2 (Eplg2), including 5'- and 3'-flanking sequences. Restriction mapping, coupled with Southern blot hybridization and sequencing, was used to determine the structural organization of the gene. The Eplg2 genomic locus spans a region of approximately 12 kb, encoding five exons and four introns. The first intron comprises approximately 8.5 kb of the entire 12-kb genomic sequence. Eplg2 was mapped to the mouse X chromosome by interspecific backcross analysis and is tightly linked to the androgen receptor (Ar) locus.

Amino Acid Sequence↗
PubMed1994

Characterization of the mouse loricrin gene: linkage with profilaggrin and the flaky tail and soft coat mutant loci on chromosome 3.

Loricrin is the major component of a specialized structure, termed the cornified cell envelope, that is formed beneath the plasma membrane of stratified squamous epithelial cells and is coexpressed with profilaggrin in terminally differentiating epidermal keratinocytes. Full-length cDNAs for both mouse and human loricrin have been cloned and characterized, as has the human gene. Here we report the isolation and characterization of the mouse loricrin gene. The gene has a simple structure consisting of a single intron of 1091 bp within the 5' noncoding sequence and an uninterrupted open reading frame. Using PCR analyses of DNAs isolated from mouse x Chinese hamster somatic cell hybrids, we have mapped both the loricrin and the profilaggrin genes to chromosome 3. Genetic linkage analysis has shown that mouse loricin and profilaggrin lie within 1.5 +/- 1.1 centimorgans of each other. We have further shown that both genes map in the vicinity of the flaky tail (ft) and soft coat (soc) loci. These mouse mutants exhibit a number of changes in their integument, suggesting that abnormalities in these genes may contribute to the mutant phenotype.

Amino Acid Sequence↗
PubMed1994

Characterization of the genomic structure, chromosomal location, promoter, and development expression of the alpha-globin transcription factor CP2.

We recently cloned murine and human cDNAs that encode CP2, a cellular transcription factor that interacts with the alpha-globin promoter as well as with additional cellular and viral promoter elements. We have now characterized the genomic structure, chromosome location, promoter, and expression pattern of the factor. Genes for the murine and human mRNAs contained 16 and 15 exons, respectively. Both genes spanned approximately 30 kilobases of chromosomal DNA, and among coding exons, all exon/intron boundaries were conserved. The human gene for CP2 was found to reside on chromosome 12 while the murine gene mapped to the distal end of chromosome 15, near Gdc-1, Wnt-1, and Rarg, a region syntenic with human chromosome 12. The murine and human promoters initiated mRNAs at multiple start sites in a conserved region that spanned more than 450 nucleotides. Lastly, a study of the pattern of CP2 gene expression showed that the factor was expressed in all adult and fetal murine tissues examined from at least day 9.5 of development.

Amino Acid Sequence↗
PubMed1994

Assignment of two alpha 2 adrenoceptor subtype genes to murine chromosomes.

Subtype-specific probes to the murine homologs of the human ADRA2B and ADRA2C genes were prepared by PCR amplification and used to map these two genes to mouse chromosomes 2 and 5, respectively. Both genes mapped in regions of mouse chromosomes consistent with their map location in humans. These mapping results provide additional insights into the linkage relationships among members of this important gene family.

Animals↗
PubMed1994

The mouse CD69 gene. Structure, expression, and mapping to the NK gene complex.

CD69 is a rapidly induced T cell activation Ag that is also expressed in an inducible fashion on cells of most, if not all, hematopoietic lineages. Molecular cloning has shown that CD69 is a type II membrane glycoprotein that is a member of the C-type lectin family. In this report we have shown that induction of CD69 mRNA in activated murine thymocytes and T cells is very rapid, peaking between 30 and 60 min poststimulation, and transient, dropping to nearly resting levels by 8 h. An analysis of the mouse CD69 gene structure showed the gene to consist of 5 exons and have a phorbol ester-inducible promoter element within the first 700 bp upstream of the start of transcription. Chromosomal mapping placed the mouse CD69 gene on the long arm of chromosome 6 near the NK gene complex that contains the related NKR-P1 and Ly-49 gene families. The human CD69 gene mapped to chromosome 12p13 near the related NKG2 gene cluster and in a region associated with rearrangements in approximately 10% of cases of childhood acute lymphocytic leukemia.

Amino Acid Sequence↗
PubMed1994

Mouse alpha N-catenin: two isoforms, specific expression in the nervous system, and chromosomal localization of the gene.

We isolated cDNAs encoding mouse homologues of chicken alpha N-catenin, a protein associated with the cadherin cell adhesion molecules, and identified two isoforms of this protein. One isoform (alpha N-catenin I) was identical to the chicken alpha N-catenin that had previously been identified, and the other (alpha N-catenin II) differed in having a 48-amino acid insertion in its C-terminal region. The ratio of the two isoforms changed during development; the isoform II was more abundant than the other in earlier embryonic stages, whereas isoform I was predominant in the adult stage. Immunostaining and in situ hybridization analyses revealed that the mouse alpha N-catenin was expressed almost exclusively in the nervous system. During embryogenesis, alpha N-catenin was first detected in nerve fibers of cranial and dorsal root ganglia and also in early neurons in the neural tube, including motor neurons. Thereafter, the expression of this protein occurred in various regions of the nervous system. Neurons, in general, strongly expressed alpha N-catenin, especially in their axonal fibers. On the other hand, the expression in glial cells varied with the region. For example, the ependymal layers of the neural tube generally expressed low levels of alpha N-catenin except at the inner limiting membrane facing the central canal, whereas the floor and roof plate exhibited strong expression of this protein at various portions of the central nervous system. The choroid plexus was devoid of alpha N-catenin. In the alpha N-catenin-negative regions, another subtype of alpha-catenin, alpha E-catenin, was expressed. Concerning nonneural tissues, alpha N-catenin was expressed only in some local mesenchymal cell clusters and the lens fibers. These results suggest that alpha N-catenin plays specific roles in neural cell-cell interactions. We also localized the mouse alpha N-catenin gene to chromosome 6.

Amino Acid Sequence↗
PubMed1994

Voltage-gated potassium channel genes are clustered in paralogous regions of the mouse genome.

Cloning of the Drosophila Shaker gene established that a neurological phenotype including locomotor dysfunction can be caused by a mutation in a voltage-gated potassium (K) channel gene. Shaker sequences have been used to isolate a large family of related K channel genes from both flies and mammals. Toward elucidating the evolutionary relationship between loci and the potential causal connection that K channels may have to mammalian genetic disorders, we report here the genetic mapping of 12-16 different murine, voltage-gated K channel genes. We find that multiple genes, in some cases from distantly related K channel subfamilies, occur in clusters in the mouse genome. These mapping results suggest that the K channel gene subfamilies arose through ancient localized gene duplication events, followed by chromosomal duplications and rearrangements as well as further gene duplication. We also note that several neurologic disorders of both mouse and human are associated with the chromosomal regions containing K channel genes.

Animals↗
PubMed1994

The genomic structure of an insertional mutation in the dystonia musculorum locus.

We have previously identified a line of transgenic mice, Tg4, in which an hsp68-lacZ hybrid gene has inserted into the dystonia musculorum (dt) locus on chromosome 1. We have confirmed the localization of the Tg4 integration site to the proximal region of mouse chromosome 1 by interspecific backcross analysis. One end of the integration complex has been cloned and we have used single-copy probes from the flanking region to screen a mouse genomic library. Several overlapping lambda phage clones have been isolated and arranged into a contig spanning 75 kb of genomic DNA. Probes from the genomic contig have enabled us to characterize the wildtype and Tg4 loci. We report that the integration of the transgene was accompanied by a deletion of 45 kb of host genomic sequences with no other detectable rearrangement in the Tg4 genome.

Animals↗
PubMed1994

Organization, expression, and chromosomal location of the mouse insulin-like growth factor binding protein 5 gene.

Insulin-like growth factor binding proteins (IGFBPs) constitute a family of at least six secreted proteins that bind insulin-like growth factors I and II (IGF-I and -II) and are capable of modifying IGF actions on target cells. We previously have purified an approximately 29-kDa IGFBP that is secreted by myoblasts during their terminal differentiation, have identified the protein as mouse IGFBP-5, and have cloned its cDNA (James et al., 1993). In this study, we have characterized the mouse IGFBP-5 gene, established its pattern of expression in the adult mouse, and defined its chromosomal location. The 17-kb gene was isolated on overlapping cosmid and lambda clones, and the four exons encoding the 5914-bp mRNA were sequenced. The 5' end of the gene was mapped by solution-hybridization ribonuclease protection assay to two discrete sites in exon 1 that were separated by 21 bp. The relative use of each transcription start site was found to vary among different mouse tissues. By interspecies backcross mapping using progeny derived from matings of [(C57BL/6J X Mus spretus)F1 x C57BL/6J] mice, the IGFBP-5 gene was localized to the proximal region of chromosome 1 in tight linkage with fibronectin 1 (0 recombinants in 168 mice analyzed). Since this part of chromosome 1 shares homology with human chromosome 2q, and since fibronectin has been mapped to 2q34-q36, it is likely that human IGFBP-5 will reside on 2q as well. Characterization of the mouse IGFBP-5 gene now provides a starting point for studying the roles and regulation of this protein in development.

Amino Acid Sequence↗
PubMed1994

The gene for the retinal pigment epithelium-specific protein RPE65 is localized to human 1p31 and mouse 3.

The human and murine chromosomal localization for the gene for the retinal pigment epithelium-specific protein RPE65 was determined. Using interspecific backcross analysis, we mapped Rpe65 to the distal end of mouse chromosome 3. In the human, using a human-hamster hybrid panel, RPE65 was mapped to chromosome 1. By the use of fluorescence in situ hybridization, this localization was refined to 1p31. The mouse and human loci for this potential candidate gene for hereditary retinal disease do not match those of any known disease in mouse or man.

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