ABSTRACT
BACKGROUND: Appropriate search strategies are essential to ensure the integrity and reproducibility of systematic and scoping reviews, as researchers seek to capture as many relevant resources as possible. In the case of Indigenous health reviews, researchers are met with the special challenge of creating a search strategy that can encompass this large, diverse population group with no universally agreed upon identification criteria. MAIN BODY: With an aim to promote improved review methodologies that uphold standards of justice, autonomy, and equity for Indigenous peoples and other heterogeneous populations, we describe critical gaps and approaches to close them. We report organizational and transparency issues around how Indigenous populations are indexed in several major databases, and draw on examples of published reviews and protocols to demonstrate the challenges inherent to creating a comprehensive search strategy. CONCLUSIONS: The conduct and communication of results from health literature research on global Indigenous populations are compromised by challenges of methodology that are rooted in the complexities inherent to defining Indigenous peoples. These challenges must be urgently addressed to improve this important field of inquiry moving forward.
Subject(s)
Indigenous Peoples , Population Groups , Humans , Reproducibility of Results , Review Literature as TopicABSTRACT
Using homology-based database screening, we have identified the mouse homologue for the recently described matrix metalloproteinase-19 (MMP-19). Sequencing of mouse MMP-19 resulted in a putative open reading frame (ORF) of 527 amino acids showing 84% identity to the human homologue. In mouse, MMP-19 appears to be most highly expressed in the liver; however, there is a detectable level of expression in all tissues analyzed. The major mouse MMP-19 transcript is almost twice as long as that of human. The COOH-terminal serine and threonine-rich domain is considerably longer in the mouse homologue. The mouse MMP-19 gene maps to very distal end of mouse chromosome 10.
Subject(s)
Gene Expression Regulation, Enzymologic , Metalloendopeptidases/genetics , Metalloendopeptidases/metabolism , Amino Acid Sequence , Animals , Base Sequence , Catalytic Domain , Chromosome Mapping , Cloning, Molecular , Humans , Liver/physiology , Matrix Metalloproteinases, Secreted , Mice , Mice, Inbred Strains , Molecular Sequence Data , Sequence Analysis , Sequence Homology, Amino AcidABSTRACT
Enamelysin is a recently isolated member of the matrix metalloproteinase (MMP) family of extracellular matrix (ECM)-degrading enzymes. Here we describe the isolation and characterization of the mouse enamelysin cDNA. Expression of mouse enamelysin was detectable only in ameloblasts and odontoblasts of developing teeth. Characterization of mouse enamelysin demonstrated that it is highly conserved in both its sequence content and pattern of expression relative to the porcine, human, and bovine homologues previously described.
Subject(s)
Cloning, Molecular/methods , Gene Expression Regulation, Enzymologic/genetics , Matrix Metalloproteinases/genetics , Amino Acid Sequence , Animals , Base Sequence , Blotting, Northern/methods , Cattle , DNA, Complementary/genetics , Humans , In Situ Hybridization/methods , Matrix Metalloproteinase 20 , Mice , Molar/enzymology , Molecular Sequence Data , Polymerase Chain Reaction/methods , Sequence Analysis, DNA , Sequence Homology, Amino Acid , SwineABSTRACT
To understand the biologic function of TIMP-2, a member of the tissue inhibitors of metalloproteinases family, an inactivating mutation was introduced in the mouse Timp-2 gene by homologous recombination. Outbred homozygous mutants developed and procreated indistinguishably from wild type littermates, suggesting that fertility, development, and growth are not critically dependent on TIMP-2. Lack of functional TIMP-2, however, dramatically altered the activation of proMMP-2 both in vivo and in vitro. Fully functional TIMP-2 is essential for efficient activation of proMMP-2 in vivo. No evidence of successful functional compensation was observed. The results illustrate the duality of TIMP-2 function, i.e. at low concentrations, TIMP-2 exerts a "catalytic" or enhancing effect on cell-mediated proMMP-2 activation, whereas at higher concentrations, TIMP-2 inhibits the activation and/or activity of MMP-2.
Subject(s)
Enzyme Precursors/metabolism , Gelatinases/metabolism , Metalloendopeptidases/metabolism , Tissue Inhibitor of Metalloproteinase-2/genetics , Amino Acid Sequence , Animals , Base Sequence , Cells, Cultured , Enzyme Activation , Female , Male , Mice , Molecular Sequence Data , Mutagenesis, Site-Directed , Protein Structure, Secondary , Recombination, Genetic , Tissue Inhibitor of Metalloproteinase-2/metabolismABSTRACT
Mouse enamelysin (Mmp20), a member of the matrix metalloproteinase (MMP) family of extracellular matrix degrading enzymes, shows a high degree of homology with other MMPs, particularly those of the stromelysin/collagenase subfamilies. It is expressed exclusively in ameloblasts and odontoblasts. The mouse enamelysin gene (Mmp20) is made up of 10 exons spanning approximately 65 kb within the MMP gene cluster at the centromeric end of chromosome 9.
Subject(s)
Chromosome Mapping , Matrix Metalloproteinases/chemistry , Matrix Metalloproteinases/genetics , Animals , Cloning, Molecular , DNA Primers/chemistry , Exons/genetics , Gene Expression Regulation , Genetic Markers , Introns/genetics , Matrix Metalloproteinase 20 , Matrix Metalloproteinases/biosynthesis , Matrix Metalloproteinases/isolation & purification , Mice , Mice, Inbred C57BL , Molecular Sequence Data , Multigene Family/genetics , MuridaeABSTRACT
MT1-MMP is a membrane-bound matrix metalloproteinase (MT-MMP) capable of mediating pericellular proteolysis of extracellular matrix components. MT1-MMP is therefore thought to be an important molecular tool for cellular remodeling of the surrounding matrix. To establish the biological role of this membrane proteinase we generated MT1-MMP-deficient mice by gene targeting. MT1-MMP deficiency causes craniofacial dysmorphism, arthritis, osteopenia, dwarfism, and fibrosis of soft tissues due to ablation of a collagenolytic activity that is essential for modeling of skeletal and extraskeletal connective tissues. Our findings demonstrate the pivotal function of MT1-MMP in connective tissue metabolism, and illustrate that modeling of the soft connective tissue matrix by resident cells is essential for the development and maintenance of the hard tissues of the skeleton.
Subject(s)
Arthritis/genetics , Bone Diseases, Metabolic/genetics , Collagen/metabolism , Connective Tissue Diseases/genetics , Dwarfism/genetics , Matrix Metalloproteinases/genetics , Metalloendopeptidases , Animals , Arthritis/mortality , Arthritis/pathology , Body Constitution , Bone Development , Bone Diseases, Metabolic/mortality , Bone Diseases, Metabolic/pathology , Bone Resorption/pathology , Cachexia/genetics , Cartilage/pathology , Connective Tissue Diseases/mortality , Connective Tissue Diseases/pathology , Disease Models, Animal , Dwarfism/mortality , Dwarfism/pathology , Fibrosis , Growth Plate/pathology , Hyalin , Matrix Metalloproteinase 14 , Matrix Metalloproteinases/metabolism , Matrix Metalloproteinases, Membrane-Associated , Mice , Mice, Knockout , Osteoblasts/enzymology , Osteoblasts/pathology , Skin/cytology , Skin/enzymology , Skull/pathology , Stromal Cells/pathology , Synovial Membrane/pathologySubject(s)
Tissue Inhibitor of Metalloproteinase-2/genetics , Animals , Base Sequence , Cells, Cultured , Chromosome Deletion , Concanavalin A/pharmacology , Enzyme Activation , Fibroblasts/metabolism , Gelatinases/metabolism , Matrix Metalloproteinase 2 , Metalloendopeptidases/metabolism , Mice , Mice, Knockout , Molecular Sequence Data , Mutagenesis , Recombination, Genetic , Tissue Inhibitor of Metalloproteinase-2/deficiencyABSTRACT
DNase I hypersensitive site 2 (HS 2) of the human beta-globin Locus Control Region (LCR) directs high level expression of the beta-globin gene located 50 kilobases downstream. Experiments in cultured cells and in transgenic mice demonstrate that duplicated AP1-like sites in HS 2 are required for this powerful enhancer activity. A cDNA clone encoding a basic, leucine-zipper protein that binds to these sites was isolated and designated Locus Control Region-Factor 1 (LCR-F1). This protein is a member of a new family of regulatory factors that contain a 63 amino acid 'CNC domain' overlapping the basic region. This domain is approximately 70% identical in the Drosophila Cap N Collar (CNC) protein, NF-E2 and LCR-F1. LCR-F1 transactivates an HS 2/gamma-globin reporter gene over 170-fold in transient transfection experiments specifically in erythroid cells. These results suggest that LCR-F1 may be a critical factor involved in LCR-mediated, human globin gene expression.
Subject(s)
Erythrocytes/metabolism , Gene Expression Regulation , Globins/genetics , Transcription Factors/genetics , Animals , Base Sequence , Binding Sites , Cloning, Molecular , DNA , DNA-Binding Proteins/genetics , DNA-Binding Proteins/metabolism , Erythroid-Specific DNA-Binding Factors , Globins/biosynthesis , HeLa Cells , Humans , Leukemia, Erythroblastic, Acute , Mice , Mice, Transgenic , Molecular Sequence Data , Mutation , NF-E2 Transcription Factor , NF-E2 Transcription Factor, p45 Subunit , NF-E2-Related Factor 1 , Recombinant Fusion Proteins/genetics , Recombinant Fusion Proteins/metabolism , Sequence Homology, Amino Acid , Transcription Factors/metabolism , Tumor Cells, CulturedABSTRACT
The human beta-globin Locus Control Region (LCR) has two important activities. First, the LCR opens a 200 kb chromosomal domain containing the human epsilon-, gamma- and beta-globin genes and, secondly, these sequences function as a powerful enhancer of epsilon-, gamma- and beta-globin gene expression. Erythroid-specific, DNase I hypersensitive sites (HS) mark sequences that are critical for LCR activity. Previous experiments demonstrated that a 1.9 kb fragment containing the 5' HS 2 site confers position-independent expression in transgenic mice and enhances human beta-globin gene expression 100-fold. Further analysis of this region demonstrates that multiple sequences are required for maximal enhancer activity; deletion of SP1, NF-E2, GATA-1 or USF binding sites significantly decrease beta-globin gene expression. In contrast, no single site is required for position-independent transgene expression; all mice with site-specific mutations in 5' HS 2 express human beta-globin mRNA regardless of the site of transgene integration. Apparently, multiple combinations of protein binding sites in 5' HS 2 are sufficient to prevent chromosomal position effects that inhibit transgene expression.
Subject(s)
Deoxyribonuclease I/metabolism , Enhancer Elements, Genetic , Gene Expression , Globins/genetics , Animals , Base Sequence , Binding Sites , DNA-Binding Proteins/metabolism , Erythroid-Specific DNA-Binding Factors , GATA1 Transcription Factor , Gene Deletion , Humans , Mice , Mice, Transgenic , Molecular Sequence Data , Mutagenesis, Site-Directed , NF-E2 Transcription Factor , NF-E2 Transcription Factor, p45 Subunit , Regulatory Sequences, Nucleic Acid , Sp1 Transcription Factor/metabolism , Transcription Factors/metabolism , Upstream Stimulatory FactorsABSTRACT
The human beta-globin locus control region (LCR) is essential for high-level expression of human epsilon-, gamma-, and beta-globin genes. Developmentally stable DNase I hypersensitive sites (designated HS) mark sequences within this region that are important for LCR activity. A 1.9-kilobase (kb) fragment containing the 5' HS 2 site enhances human beta-globin gene expression 100-fold in transgenic mice and also confers position-independent expression. To further define important sequences within this region, deletion mutations of the 1.9-kb fragment were introduced upstream of the human beta-globin gene, and the constructs were tested for activity in transgenic mice. Although enhancer activity was gradually lost with deletions of both 5' and 3' sequences, a 373-base-pair (bp) fragment retained the ability to confer relative position-independent expression. Three prominent DNase I footprints were observed in this region with extracts from the human erythroleukemia cell line K-562, one of which contained duplicated binding sites for transcription factor AP-1 (activator protein 1). When the 1.9-kb fragment containing an 18-bp deletion of the AP-1 binding sites was tested in transgenic mice, enhancer activity decreased 20-fold but position-independent expression was retained.
