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Biomedical subjects

B L Hogan

Publications and source records attributed to B L Hogan.

At least 127 records · Page 7Linked to original sources
PubMed1990

Location of the gene involving the small eye mutation on mouse chromosome 2 suggests homology with human aniridia 2 (AN2).

Using an interspecific backcross, we have mapped the gene involved in the mouse Small eye mutation (SeyMH) relative to six cloned markers on chromosome 2 (Hox-5.1, Cas-1, Fshb, Bmp-2a, and ld) and the agouti locus. The results suggest that the Sey gene maps between Fshb and Cas-1. Human mapping studies have shown that the aniridia (AN2) gene, which is part of the Wilms tumor susceptibility, aniridia, genitourinary abnormalities, and mental retardation (WAGR) complex, is also between FSHB and CAT on human chromosome 11. The conserved linkage of the cloned markers and the similarity of the Sey/+ and AN2/+ phenotypes suggest that the gene involved in the Sey mutation is the mouse homolog of the human AN2 gene.

Animals↗
PubMed1990

Growth factor-regulated proteases and extracellular matrix remodeling during mammalian development.

Although specific details may vary from system to system, some general concepts have emerged from studies of the regulation of ECM components, proteases, and protease inhibitors by growth factors. Growth factors may be divided into those that enhance matrix synthesis and inhibit matrix degradation and those that stimulate protease production and result in a general degradation of ECM. These relationships are illustrated in Fig. 3. In general, growth factors such as EGF, PDGF, bFGF, and IL-1 induce genes for ECM-degrading proteinases and their activators (e.g., metalloproteinases and PAs). This concerted release of proteases results in the degradation of the many components of basement membranes or ECM. Other growth factors (e.g., the TGF-beta family) stimulate the synthesis of ECM structural proteins (e.g., collagens and fibronectin), elevate levels of inhibitors of proteases (e.g., TIMP and PAI-1), and repress expression of the matrix-degrading metalloproteinases and PA. The overall result is systems in which such a relationship seems very likely. Direct evidence should become available within the next few years now that the technology exists to correlate spatial and temporal expression of growth factors with expression of ECM-associated proteases and inhibitors and to misregulate this expression in specific ways, for example, in transgenic mice. Future studies involving the use of model systems in which complex tissue interactions and organogenesis can be followed in culture should also provide the opportunity to examine cause-and-effect relationships between growth factors and ECM-modulating proteins.

Animals↗
PubMed1990

Molecular and genetic characterization of a radiation-induced structural rearrangement in mouse chromosome 2 causing mutations at the limb deformity and agouti loci.

Molecular characterization of mutations in the mouse, particularly those involving agent-induced major structural alterations, is proving to be useful for correlating the structure and expression of individual genes with their function in the whole organism. Here we present the characterization of a radiation-induced mutation that simultaneously generated distinct alleles of both the limb deformity (ld) and agouti (a) loci, two developmentally important regions of chromosome 2 normally separated by 20 centimorgans. Cytogenetic analysis revealed that an interstitial segment of chromosome 17 (17B- 17C; or, possibly, 17A2-17B) had been translocated into the distal end of chromosome 2, resulting in a smaller-than-normal chromosome 17 (designated 17del) and a larger form of chromosome 2 (designated 2(17). Additionally, a large interstitial segment of the 2(17) chromosome, immediately adjacent and proximal to the insertion site, did not match bands 2E4-2H1 at corresponding positions on a normal chromosome 2. Molecular analysis detected a DNA rearrangement in which a portion of the ld locus was joined to sequences normally tightly linked to the a locus. This result, along with the genetic and cytogenetic data, suggests that the alleles of ld and a in this radiation-induced mutation, designated ldIn2 and ajIn2, were associated with DNA breaks caused by an inversion of an interstitial segment in the 2(17) chromosome.

Abnormalities, Radiation-Induced↗
PubMed1990

Indirect fluorometric detection of tryptic digests separated by capillary zone electrophoresis.

This work demonstrates the analytical utility of indirect fluorescence detection with capillary zone electrophoresis (CZE) for the analysis of trace quantities of macromolecular mixtures. Detection is based upon charge displacement and is not based upon any absorption or emission property of the analyte. No derivatization step is required. Indirect fluorescence is therefore a general detector for electrophoresis. Subfemtomolar quantities of tryptic digest mixtures are separated within three minutes, and reproducible peaks are obtained from the mixtures. Mass limits of detection are 3000 times lower than those of commercial high-performance liquid chromatography (HPLC) UV absorbance detectors and 180 times lower than those of UV absorbance detectors in CZE systems. This separation and detection system should be well suited to analysis of trace quantities of mixtures of peptides.

Caseins↗
PubMed1990

Organogenesis and pattern formation in the mouse: RNA distribution patterns suggest a role for bone morphogenetic protein-2A (BMP-2A).

Bone morphogenetic protein-2A (BMP-2A) is a member of the transforming growth factor beta (TGF beta) gene family that has been implicated in cartilage and bone formation. Here we use in situ hybridization to show that BMP-2A RNA is expressed in a variety of embryonic epithelial and mesenchymal tissues outside of the developing skeletal system, including cell populations known to play important roles in morphogenesis. Thus, high levels of transcripts are found in developing limb buds (ventral ectoderm and apical ectodermal ridge), heart (myocardium of the atrioventricular canal), whisker follicles (ectodermal placodes, hair matrix and precortex cells), tooth buds (epithelial buds, dental papilla and odontoblasts), and craniofacial mesenchyme, as well as a number of other sites. The expression patterns of BMP-2A are different from those of TGF beta-1, -2 and -3, and this is illustrated in detail in the developing whisker follicles. These results suggest that BMP-2A plays multiple roles in morphogenesis and pattern formation in the vertebrate embryo.

Animals↗
PubMed1990

In situ hybridization analysis of TGF beta 3 RNA expression during mouse development: comparative studies with TGF beta 1 and beta 2.

To date, three closely-related TGF beta genes have been found in the mouse; TGF beta 1, TGF beta 2 and TGF beta 3. Previous experiments have indicated that TGF beta 1 and TGF beta 2 may play important roles during mouse embryogenesis. The present study now reports the distribution of transcripts of TGF beta 3 in comparison to the other two genes and reveals overlapping but distinct patterns of RNA expression. TGF beta 3 RNA is expressed in a diverse array of tissues including perichondrium, bone, intervertebral discs, mesenteries, pleura, heart, lung, palate, and amnion, as well as in central nervous system (CNS) structures such as the meninges, choroid plexus and the olfactory bulbs. Furthermore, in several organ systems, TGF beta 3 transcripts are expressed during periods of active morphogenesis suggesting that the protein may be an important factor for the growth and differentiation of many embryonic tissues.

Animals↗
PubMed1989

Evidence for positive and negative regulatory elements in the 5'-flanking sequence of the mouse sparc (osteonectin) gene.

We have investigated the role of 5'-flanking DNA sequences in regulating the expression of the murine Sparc (osteonectin) gene in parietal endoderm cells and in F9 embryonal carcinoma cells induced to differentiate into parietal endoderm with retinoic acid and cyclic AMP. Varying lengths of flanking sequences extending up to 3.0 kilobase pairs 5' of the transcription initiation site were linked to the bacterial chloramphenicol transacetylase gene in the Bluescript M13- vector. The constructs were tested in transient assays, using a beta-galactosidase plasmid as a transfection control. Sequences between 78 and 169 base pairs upstream of the cap site are the minimum required for cell-type specific promoter activity; this region is dominated by two oligopurine/oligopyrimidine stretches or "GAGA" boxes and is highly conserved between the mouse and bovine genes. Addition of the sequence between -169 and -449, which includes part or all of a third GAGA box, results in increased parietal endoderm specific transcription, up to a maximum of 6.3-fold higher than in undifferentiated F9 cells. Further addition of sequences between -449 and -638 markedly reduces promoter activity in both cell types but parietal endoderm-specific activity is restored in constructs containing 2.2 and 3.0 kilobase pairs of flanking DNA. In addition, we have identified sequences related to the consensus sequence for steroid response elements, one of which is able to confer progesterone-enhanced transcription when tested with a heterologous promoter in steroid responsive cells. These results suggest that negative and positive elements normally interact to regulate the temporal and tissue-specific patterns of Sparc gene transcription seen in vivo.

Animals↗
PubMed1989

Distribution of expression of 2AR (osteopontin) in the embryonic mouse inner ear revealed by in situ hybridisation.

Using in situ hybridisation we have determined the distribution of expression of 2ar (also known as osteopontin, bone sialoprotein 1 or 44-kDa bone phosphoprotein) in the developing mouse inner ear. We have identified several discrete sites, both osteogenic and non-osteogenic, that express 2ar from embryonic day 16.5 (E16.5). In addition to the regions of developing bone of the calvaria and temporal bone, we have found 2ar expression in the epithelium of the sensory maculae (but not in the organ of Corti), in the vestibular and auditory ganglia and nerves (but not in the nerves that innervate the whiskers in the snout), in the epithelium that lines the endolymphatic sac (but not in the neighbouring and contiguous endolymphatic duct) and also in the epithelium that lines the semicircular canals. We found also individual cells scattered throughout the brain, loose mesenchyme and blood vessels of the head that were expressing 2ar. Several of the sites in the inner ear, for example the maculae and the endolymphatic sac, are known to be involved in the production of calcified matrix. The results extend the range of tissue types known to express the protein and demonstrate that tissues of histologically similar appearance can nonetheless differ in their gene expression.

Animals↗
PubMed1989

Localization of the mouse gene for secreted phosphoprotein 1 (Spp-1) (2ar, osteopontin, bone sialoprotein 1, 44-kDa bone phosphoprotein, tumor-secreted phosphoprotein) to chromosome 5, closely linked to Ric (Rickettsia resistance).

We have used a cDNA probe for mouse secreted phosphoprotein 1 (Spp-1, also known as 2ar, osteopontin, bone sialoprotein 1, 44-kDa bone phosphotein, tumor-secreted protein) to find a restriction fragment length polymorphism in the gene from C57BL/6J and DBA/2J mice. The strain distribution pattern in 25 BXD recombinant inbred lines is identical with that previously determined for the dominant, autosomal gene, Ricr (Rickettsia resistance). This places Spp-1 on mouse chromosome 5 with a 95% confidence limit of being within 4.32 cM of Ric. Evidence supporting the possibility of allelism between Spp-1 and Ric is briefly discussed.

Animals↗
PubMed1989

Vgr-1, a mammalian gene related to Xenopus Vg-1, is a member of the transforming growth factor beta gene superfamily.

The transforming growth factor beta (TGF-beta)-related products of the Xenopus Vg-1 and Drosophila decapentaplegic (DPP) genes have been implicated in the control of growth and differentiation during embryogenesis. We have isolated a mouse cDNA, Vgr-1, that encodes a polypeptide structurally related to Xenopus Vg-1. Sequence comparisons indicate that the Vgr-1 protein belongs to a family of DPP-like gene products within the TGF-beta superfamily. The levels of Vgr-1 RNA were determined in embryos and tissues isolated at various stages of development. A 3.5-kilobase mRNA increases throughout development and into adulthood in many tissues and in F9 teratocarcinoma cells differentiating into endoderm in response to retinoic acid and cAMP. The amino acid homologies and patterns of expression suggest that, like the DPP gene product, Vgr-1 plays a role at various stages of development.

Aging↗
PubMed1989

Patterns of expression of murine Vgr-1 and BMP-2a RNA suggest that transforming growth factor-beta-like genes coordinately regulate aspects of embryonic development.

The murine Vgr-1 (Vg-related) and BMP-2a (bone morphogenetic protein 2a) genes are members of the decapentaplegic subgroup of the transforming growth factor-beta (TGF beta) superfamily. Although genetic and biochemical studies suggest that the members of this subgroup play important roles in development, little is known about their function in mammals. Therefore, we investigated the expression of Vgr-1 and BMP-2a RNAs in embryonic, newborn, and adult tissues by in situ hybridization. Vgr-1 RNA is maternally encoded in ovarian oocytes but declines in fertilized eggs and is undectable by the two- to four-cell stage. Only low levels of transcripts are seen in blastocysts and early postimplantation stages. From mid-gestation on, Vgr-1 RNA is expressed at high levels in developing skin, especially in the suprabasal cells of the proliferating epidermis but not in the dermis or hair follicles, both of which contain TGF beta 1 and/or TGF beta 2 RNAs. In contrast, BMP-2a transcripts are seen only in the hair follicles in the cells of the hair bulb cortex. Temporally and spatially distinct patterns of BMP-2a, Vgr-1, TGF beta 1, and TGF beta 2 expression are also seen in different populations of mesenchymal cells in the developing skeletal system (cartilage and bone). Our results suggest that the coordinated expression of several members of the TGF beta superfamily is required to control the progression of specific cell types through their differentiation pathways.

Animals↗
PubMed1989

Developmental expression of tissue inhibitor of metalloproteinase (TIMP) RNA.

Single-stranded antisense RNA probes have been used to study the expression of the metalloproteinase inhibitor TIMP (tissue inhibitor of metalloproteinases), during mouse embryogenesis and in adult tissues. Using a sensitive RNase protection assay, low levels of transcript can be detected in a variety of tissues, including maternal deciduum, embryonic kidney, lung and amnion. Higher levels are seen in osteogenic tissues such as calvaria, while the highest level in any tissue is found in the ovary, though even here expression is an order of magnitude below that observed in growth factor-treated fibroblasts in vitro. Using the technique of in situ hybridization, TIMP transcripts can first be detected in osteogenic tissues in the head and limb at about 15.5 days post coitum, and increase in amount until birth. The high levels of TIMP RNA in the ovary are localized to cells of the corpora lutea.

Animals↗
PubMed1989

Expression of transforming growth factor beta 2 RNA during murine embryogenesis.

We have studied the temporal and spatial expression of transforming growth factor beta 2 (TGF beta 2) RNA in mouse embryos from 10.5 days post coitum (p.c.) to 3 days post partum (p.p.) by in situ hybridization analysis. TGF beta 2 RNA is expressed in a variety of tissues including bone, cartilage, tendon, gut, blood vessels, skin and fetal placenta, and is in general found in the mesenchymal component of these tissues. The expression of TGF beta 2 RNA changes during development in a manner consistent with a role for the gene product in mediating mesenchymal-epithelial interactions.

Animals↗
PubMed1989

Expression of genes for non-collagenous proteins during embryonic bone formation.

In situ hybridization has been used to localize RNAs for a variety of non-collagenous proteins during embryogenesis of the mouse, with particular reference to bone formation. Transcripts of the Sparc (osteonectin) gene are first detected around 14.5d post coitum (p.c.) in the periosteal layer around the cartilage model of long bones and in membrane bone in the head. By 15.5d p.c. transcripts are seen in hypertrophic cartilage and later in cells within the bone closely associated with new matrix. By contrast, RNA for 2ar (osteopontin) is not seen in the periosteal layer but is confined to cells in the marrow region. TIMP (tissue inhibitor of metalloproteinase) transcripts show a very similar distribution to those for Sparc.

Animals↗
PubMed1988

Characterization of the mouse SPARC/osteonectin gene. Intron/exon organization and an unusual promoter region.

Two overlapping cosmids have been isolated containing the entire murine gene for SPARC (osteonectin), a Ca2+-binding, phosphorylated glycoprotein associated with extracellular matrix synthesis and remodeling. The gene contains 10 exons and covers 26.5 kilobase pairs of DNA. Exon analysis shows that the two N-terminal glutamic acid-rich sequences which are predicted to undergo conformational change upon binding of calcium, as well as the C-terminal EF-hand Ca2+-binding domain are each encoded by a single exon. Comparative analysis of the exon sequence does not support the idea that the SPARC gene has evolved by shuffling of exons from other Ca2+-binding proteins. The 5' flanking region of the SPARC gene, which promotes transcription when placed in front of the bacterial chloramphenicol acetyltransferase gene, contains neither "TATA" nor "CAAT" box sequences. However, unlike most other genes lacking these motifs, mapping of the 5' end of the SPARC gene by RNase protection and primer extension analysis reveals only a single major and one minor transcription start site. The upstream region to -120 includes six repeats of the sequence GGAGG, two repeats of the sequence 5' GGAGG A/C GGAGGG 3', and a potential transcription factor AP-2 binding site.

Acetyltransferases↗
PubMed1988

Temporal and tissue-specific expression of distinct retrovirus-like (VL30) elements during mouse development.

We have analyzed the expression of VL30 retroviral RNA transcripts during mouse embryogenesis. VL30 RNA was found in all tissues examined from mid-gestation, but increased dramatically at later times in the extraembryonic amnion and visceral yolk sac, and to a lesser extent in embryonic liver. The overall temporal and tissue-specific pattern of expression was unlike that of other retrotransposon gene families. S1 nuclease mapping experiments which distinguish transcripts from distinct VL30 elements suggest that they are independently regulated in different tissues during mouse development.

Animals↗