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D J Gilbert

Publications and source records attributed to D J Gilbert.

At least 271 records · Page 15Linked to original sources
PubMed1993

Cloning, expression, and chromosomal localization of the mouse meprin beta subunit.

Meprins are plasma membrane homo- or hetero-oligomeric metalloendopeptidases that contain glycosylated alpha and/or beta subunits. This paper reports the cloning and sequencing of the mouse kidney beta subunit. The primary translation product is composed of 704 amino acids which includes a transient signal sequence of 20 amino acids at the NH2 terminus. The protease domain (Asn-63 to Leu-260) contains the putative zinc-binding motif characteristic of metalloendopeptidases of the "astacin family." The COOH terminus contains an epidermal growth factor-like domain, a potential membrane-spanning domain, and an additional 26 amino acids. The beta subunit has an overall 42% identity to the alpha subunit, however, a 56-amino acid segment near the COOH terminus of alpha is missing in beta, and the putative transmembrane and cytoplasmic domains of the subunits share no significant sequence similarity. NH2-terminal analyses of detergent-solubilized mature forms revealed that, unlike alpha, the prosequence (Leu-21 to Lys-62) is not removed from the beta subunit. Northern blot analysis revealed a 2.5-kilobase message for the beta subunit in the kidney and intestine of C57BL/6 and C3H/He mice. The gene for the beta subunit was localized to mouse chromosome 18. These studies indicate that alpha and beta probably derived from a common ancestral gene, but have evolved so that their genes are on two different chromosomes, and their tissue-specific expression and post-translational processing differ.

Amino Acid Sequence↗
PubMed1993

A genetic linkage map of the mouse: current applications and future prospects.

Technological advances have made possible the development of high-resolution genetic linkage maps for the mouse. These maps in turn offer exciting prospects for understanding mammalian genome evolution through comparative mapping, for developing mouse models of human disease, and for identifying the function of all genes in the organism.

Animals↗
PubMed1993

Tissue-specific expression and chromosomal localization of the alpha subunit of mouse meprin A.

Meprins, membrane-bound oligomeric metalloendopeptidases, contain alpha and/or beta subunits. Their activities have been found in the mouse and rat kidney. The cloned cDNA for the mouse alpha subunit of meprin A (EC cloned cDNA for the mouse alpha subunit of meprin A (EC 3.4.24.18) was used here to survey mRNA expression in kidney of different mouse strains and in various tissues of mice and rats. A single message of 3.6 kilobases was found in kidney of random bred (ICR) and inbred mice (C57BL/6, DBA/2) that contain high meprin A activity and in Sprague-Dawley rat kidney. The alpha subunit message was undetectable in the kidney of C3H/He and CBA mice, inbred strains that do not express meprin A activity. Therefore, meprin A activity in the kidney of mouse strains correlates with the amount of alpha subunit mRNA present. The 3.6-kilobase mRNA meprin alpha subunit message was also detected in the small intestine of the rat but not in mice. No message was detected in brain, heart, skeletal muscle, liver, lung, or spleen of mice or rats. Polymerase chain reaction amplification or Southern blot analysis of genomic DNA revealed that the gene for the alpha subunit is present in all mouse strains as well as in human, monkey, rat, mouse, dog, cow, rabbit, and chicken, but it was not detected in yeast. There is one gene copy present in the mouse genome. The gene was localized to mouse chromosome 17 centromeric to the major histocompatibility complex (H-2) by the interspecific backcrossing method. The localization of this allele to Mep-1, the gene previously found to regulate the expression of meprin A activity in mice, supports the proposal that Mep-1 is the structural gene for the alpha subunit.

Animals↗
PubMed1993

A novel class of murine POU gene predominantly expressed in central nervous system.

A mouse gene (referred to as Emb) encoding a novel class of POU domain is described. The Emb POU domain shares only 40-50% homology to that of any other POU proteins. Nonetheless, the Emb POU domain can bind to the octamer sequence like other POU domains. Emb is a single-copy gene, located on the distal region of mouse chromosome 15. It is expressed in embryo throughout post-implantation stages, where the most prominent expression is seen in developing central nervous system. In the adult, it is highly expressed in brain, whereas weaker expression can be detected in other organs such as testis, skeletal muscle, and kidney. The expression in adult brain is most evident in neurons of hypocampus formation. Two types of Emb mRNA are expressed in brain; one type encodes a protein of 301 amino acids residues, whereas the other codes for a protein with two extra amino acids residues added at the amino-terminal end of POU domain. These two mRNA species are generated by alternative splicing by utilizing an unusual splice acceptor site: CCTCCCTCTG/. Emb mRNA expressed in testis, on the other hand, encodes a smaller protein lacking most of the amino-terminal region.

Amino Acid Sequence↗
PubMed1993

Molecular cloning, chromosomal location, and tissue-specific expression of the murine cathepsin G gene.

We previously have characterized a cluster of genes encoding cathepsin G (CG) and two other CG-like hematopoietic serine proteases, CGL-1 and CGL-2, on human chromosome 14. In this report, we clone and characterize a novel, related murine hematopoietic serine protease gene using human CG (hCG) cDNA as the probe. This murine gene spans approximately 2.5 kb of genomic DNA, is organized into five exons and four introns, and bears a high degree of homology to hCG at both nucleic acid (73%) and deduced amino acid (66%) levels. The predicted cDNA contains an open reading frame of 783 nucleotides that encodes a nascent protein of 261 amino acids. Processing of a putative signal (pre) peptide of 18 residues and an activation (pro) dipeptide would generate a mature enzyme of approximately 27 Kd that has an estimated pI of 12.0. Conserved residues at His44, Asp88, and Ser181 form the characteristic catalytic triad of the serine protease superfamily. The gene is tightly linked to the CTLA-1 locus on murine chromosome 14, where the serine protease genes mCCP1-4 are clustered. Expression of this gene is detected only in the bone marrow and is restricted to a small population of early myeloid cells. These findings are consistent with the identification of the gene encoding murine CG.

Amino Acid Sequence↗
PubMed1993

Cloning, chromosomal localization and expression pattern of the POU domain gene Oct-11.

POU domain genes encode a family of highly conserved transacting factors that influence the transcriptional activity of several cell type-specific and ubiquitous genes. We have cloned and sequenced cDNAs encoding a novel mouse POU domain protein, Oct-11, that is closely related within the POU domain to the POU class II proteins, Oct-1 and Oct-2. Recombinant Oct-11 protein binds specifically to an octamer sequence in vitro. The Oct-11 gene is expressed during mouse embryogenesis and in the adult thymus and testis. In addition, it is abundant in the myeloma cell line P3/NS-1/1-Ag4.1. We describe the structure of Oct-11 and its chromosomal localization, and discuss the evidence that the POU class II gene family has evolved by duplication and divergence of a common ancestral gene.

Amino Acid Sequence↗
PubMed1993

Chromosomal localization of mouse bullous pemphigoid antigens. BPAG1 and BPAG2: identification of a new region of homology between mouse and human chromosomes.

Two bullous pemphigoid antigens, BPAG1 and BPAG2, have been recently cloned and mapped to human chromosomes 6p12-p11 and 10q24.3, respectively. In this study, we localized the corresponding mouse genes by interspecific backcross analysis. Bpag-1 mapped to the proximal region of mouse chromosome 1, identifying a new region of homology between human chromosome 6 and mouse chromosome 1. Bpag-2 mapped to the distal end of mouse chromosome 19 in a region of homology to human chromosome 10q. These assignments confirm and extend the relationships between the human and the mouse chromosomes.

Amino Acid Sequence↗
PubMed1993

Localization of the 70-kDa peroxisomal membrane protein to human 1p21-p22 and mouse 3.

The 70-kDa peroxisomal membrane protein (PXMP1) is a member of the ATP-binding cassette transporter family. In humans, mutations in this gene may be responsible for a subset of patients with Zellweger syndrome, a lethal inborn error of peroxisome assembly. The PXMP1 gene was assigned to human chromosome 1p21-p22 by in situ hybridization and its murine homologue (Pxmp-1) to chromosome 3 by interspecific backcross analysis.

Animals↗
PubMed1993

Molecular characterization and mapping of murine genes encoding three members of the stefin family of cysteine proteinase inhibitors.

Stefins or Type 1 cystatins belong to a large, evolutionarily conserved protein superfamily, the members of which inhibit the papain-like cysteine proteinases. We report here on the molecular cloning and chromosomal localization of three newly identified members of the murine stefin gene family. These genes, designated herein as mouse stefins 1, 2, and 3, were isolated on the basis of their relatively increased expression in moth-eaten viable compared to normal congenic mouse bone marrow cells. The open reading frames of the stefin cDNAs encode proteins of approximately 11.5 kDa that show between 50 and 92% identity to sequences of stefins isolated from various other species. Data from Southern analysis suggest that the murine stefin gene family encompasses at least 6 and possibly 10-20 members, all of which appear to be clustered in the genome. Analysis of interspecific backcross mice indicates that the genes encoding the three mouse stefins all map to mouse chromosome 16, a localization that is consistent with the recent assignment of the human stefin A gene to a region of conserved homology between human chromosome 3q and the proximal region of mouse chromosome 16.

Amino Acid Sequence↗
PubMed1993

cDNA cloning and chromosomal mapping of the mouse type VII collagen gene (Col7a1): evidence for rapid evolutionary divergence of the gene.

Type VII collagen is the major component of anchoring fibrils, critical attachment structures at the dermal-epidermal basement membrane zone. Genetic linkage analyses with recently cloned human type VII collagen cDNAs have indicated that the corresponding gene, COL7A1, is the candidate gene in the dystrophic forms of epidermolysis bullosa. To gain insight into the evolutionary conservation of COL7A1, in this study we have isolated mouse type VII collagen cDNAs by screening a mouse epidermal keratinocyte cDNA library with a human COL7A1 cDNA. Two overlapping mouse cDNAs were isolated, and Northern hybridization of mouse epidermal keratinocyte RNA with one of them revealed the presence of a mRNA transcript of approximately 9.5 kb, the approximate size of the human COL7A1 mRNA. Nucleotide sequencing of the mouse cDNAs revealed a 2760-bp open reading frame that encodes the 5' half of the collagenous domain and a segment of the NC-1, the noncollagenous amino-terminal domain of type VII collagen. Comparison of the mouse amino acid sequences with the corresponding human sequences deduced from cDNAs revealed 82.5% identity. The evolutionary divergence of the gene was relatively rapid in comparison to other collagen genes. Despite the high degree of sequence variation, several sequences, including the size and the position of noncollagenous imperfections and interruptions within the Gly-X-Y repeat sequence, were precisely conserved. Finally, the mouse Col7a1 gene was located by interspecific backcross mapping to mouse Chromosome 9, a region that corresponds to human chromosome 3p21, the position of human COL7A1. This assignment confirms and extends the relationship between the mouse and the human chromosomes in this region of the genome.

Amino Acid Sequence↗
PubMed1993

The leukemia inhibitory factor receptor (LIFR) gene is located within a cluster of cytokine receptor loci on mouse chromosome 15 and human chromosome 5p12-p13.

The leukemia inhibitory factor receptor (LIFR) gene was localized to human chromosome 5p12-p13 by somatic cell hybrid analysis. Interspecific backcross analysis revealed that the murine locus was on chromosome 15 in a region of homology with human chromosome 5p. In both human and mouse genomes, the LIFR locus was linked to the genes encoding the receptors for interleukin-7, prolactin, and growth hormone.

Animals↗
PubMed1993

Identification, chromosomal location, and genome organization of mammalian G-protein-coupled receptors.

Vertebrate G-protein-coupled receptors are encoded by a diverse multigene family. Thirteen distinct G-protein-coupled receptors (Gpcr) were cloned from mouse germline cDNA following amplification in the polymerase chain reaction (PCR) with degenerate oligonucleotide primers complementary to the third and sixth transmembrane domains. Eleven Gpcr clones were mapped to single sites in the mouse genome following interspecific backcross analysis. One clone was mapped to two sites and another was not polymorphic in the cross and could not be mapped. Gpcr loci were well dispersed throughout the mouse genome and mapped to chromosomes 1, 2, 3, 4, 5, 8, 9, 10, 13, 17, and 18. Six Gpcr clones likely represent mouse homologs of already identified receptors, one Gpcr clone may identify a third type of IL-8 receptor, and three Gpcr clones appear to encode novel G-protein-coupled receptors. Further, three factor crosses and Southern blot analyses demonstrated that Gpcr16 maps proximally within the Spr deletion on mouse chromosome 1, near the Vil and Bcg loci. Human chromosomal locations for most Gpcr loci could be predicted based on linkage homologies that have been identified between human and mouse. Mapping additional G-protein-coupled receptors against the panel of murine interspecific backcrosses should expand our understanding of mammalian Gpcr gene evolution and genome organization.

Amino Acid Sequence↗
PubMed1993

The murine homologue of the human interleukin-8 receptor type B maps near the Ity-Lsh-Bcg disease resistance locus.

Interleukin-8 (IL-8), a member of the chemokine alpha subfamily, is a chemoattractant for neutrophils. Cell surface receptors for IL-8 have been cloned from rabbits and humans. Two related but different IL-8 receptors (IL-8R) have been characterized from humans. IL-8RA and IL-8RB bind IL-8 at high affinity but IL-8RB also binds GRO/MGSA and NAP-2 at high affinity. Using the human IL-8RB cDNA as a probe, we have determined that the homologous murine gene maps near the Ity-Lsh-Bcg disease resistance locus. A murine homologue of the human IL-8RB was isolated from a genomic library. This gene would encode a protein of 359 amino acids and would have a 68 and 71% amino acid identity with human IL-8RA and IL-8RB, respectively. Additional mapping data using the murine gene revealed the following genetic distances (in cM +/- 1 standard error) from the centromere: Mylf--7.9 +/- 2.7--Lsh-Ity-Bcg--1.9 +/- 1.4--Il8rb--1.9 +/- 1.4--Vil-- 5.9 +/- 2.3--Acrg--2.9 +/- 1.7--Bcl-2.

Amino Acid Sequence↗
PubMed1993

The gene for murine CTP:phosphocholine cytidylyltransferase (Ctpct) is located on mouse chromosome 16.

CTP:phosphocholine cytidylyltransferase is the rate-controlling enzyme in phosphatidylcholine biosynthesis and is essential for the survival of eukaryotic cells. The murine cDNA for the cytidylyltransferase was cloned and sequenced. A genomic clone was isolated and the chromosomal location of the Ctpct locus determined by Southern blot hybridization of DNAs from a panel of interspecific backcross progeny derived from matings of [(C57BL/6J x Mus spretus)F1 x C57BL/6J] mice. These data place the Ctpct gene on mouse chromosome 16 between the Smst and Stf-1 genes.

Amino Acid Sequence↗
PubMed1993

Susceptibility of AKXD recombinant inbred mouse strains to lymphomas.

We analyzed the susceptibility of 10 AKXD recombinant inbred (RI) mouse strains to lymphomas. These strains were derived from crosses of AKR/J, a highly lymphomatous strain, and DBA/2J, a weakly lymphomatous strain. Of the 10 strains analyzed, nine showed a high incidence of lymphoma development. As with the other 13 AKXD strains analyzed previously (M. L. Mucenski, B. A. Taylor, N. A. Jenkins, and N. G. Copeland, Mol. Cell. Biol. 6:4236-4243, 1986), the mean age at onset of lymphomas and lymphoma types varied among the strains. Whereas some strains were susceptible to T-cell lymphomas, as was the AKR/J parent, other strains were susceptible to B-cell lymphomas or to a combination of T- and B-cell lymphomas. Somatic mink cell focus-forming proviruses appeared causally associated with T-cell lymphomas, whereas somatic ecotropic proviruses appeared causally associated with B-cell lymphomas. Mice with T-cell lymphomas died significantly earlier than mice with other lymphoma types (stem, pre-B, or B cell and myeloid). The numbers of effective loci influencing the mean age at onset of lymphomas, the presence or absence of mink cell focus-forming viruses in tumors, and the frequency of T-cell lymphomas were estimated to be 3.9, 1.8, and 2.7, respectively. Tests of association with marker loci already typed in the AKXD RI strains suggested that two loci, Rmcf and Pmv-25 (or a locus linked to Pmv-25), influence all three trait variables. Finally, D21S16h, a marker locus on distal chromosome 16, showed 50% probability of linkage to a locus that influences the mean age at onset of lymphomas. Additional studies in combination with classical genetic crosses should be helpful in confirming these linkages and in identifying other loci influencing tumor susceptibility in AKXD RI strains.

Age Factors↗
PubMed1993

Chromosomal localization of the Ox-44 (CD53) leukocyte antigen gene in man and rodents.

The Ox-44 (CD53) leukocyte antigen contributes to the transduction of CD2-generated signals in T cells and natural killer (NK) cells and has been suggested to play a role in growth regulation. The gene encoding this protein was assigned to the midportion of mouse chromosome 3 by interspecific backcross mapping and to human chromosome region 1p21-->p13.3 and rat chromosome region 2q34-->q41 by fluorescence in situ hybridization. Comparative mapping data presented in this report demonstrate conservation of synteny within the region encompassing this gene in mouse (Cd53), human (CD53), and rat (CD53).

Animals↗
PubMed1993

trkC, a receptor for neurotrophin-3, is widely expressed in the developing nervous system and in non-neuronal tissues.

The Trk family of tyrosine kinases encodes receptors for nerve growth factor-related neurotrophins. Here we present a developmental expression study of trkC, which encodes a receptor for neurotrophin-3 (NT-3). Like the related genes, trk and trkB, trkC is expressed primarily in neural lineages although the pattern is complex and includes non-neuronal cells. Direct comparison with trk and trkB developmental expression patterns permits the following observations. (1) trkC is expressed in novel neural tissues where other Trk genes are silent. (2) Some tissues appear to coexpress trkB and trkC receptors in the embryo and in the adult. (3) trkC expression can be detected in the gastrulating embryo. These data provide insights into the role of Trk-family receptors and nerve growth factor-related neurotrophins during development and suggest that, in addition to regulating neuronal survival and differentiation, the neurotrophin/Trk receptor system may have broader physiological effects. Finally, interspecific mouse backcrosses have been used to map the location of each of the Trk genes on mouse chromosomes. Alignment with available chromosomal maps identify possible linkage between the Trk genes and known neurological mutations.

Animals↗