Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.2.1.23 (beta-galactosidase)
14,648 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Loss-of-function mutations in Whn (Hfh 11), a winged-helix/forkhead transcription factor, result in the nude mouse phenotype. To determine the whn expression pattern during development, we utilized mice in which a beta-galactosidase reporter gene was placed under the control of the wild-type whn promoter by homologous recombination (M. Nehls et al., 1996, Science 272, 886-889). Sites of reporter expression were confirmed by immunohistochemical staining for Whn protein or by in situ hybridization for whn mRNA. At all developmental stages, whn expression is restricted to epithelial cells. In addition to the skin and thymus, whn is expressed in the developing nails, nasal passages, tongue, palate, and teeth. In embryonic epidermis, suprabasal cells induce whn expression at the same time that terminal differentiation markers first appear. As the epidermis matures, whn promoter activity is found primarily in the first suprabasal layer, which contains keratinocytes in the early stages of terminal differentiation. In developing and mature anagen hair follicles, whn is expressed at high levels in the postmitotic precursor cells of the hair shaft and inner root sheath. Though principally associated with terminal differentiation, whn expression is also detected in progenitor cell compartments; in the hair bulb matrix and basal epidermal layer, a small subclass of cells expresses whn, while in the outer root sheath, whn promoter activity is induced as the follicle completes its elongation. Within these compartments, rare cells exhibit both whn expression and the nuclear proliferation marker Ki-67. The results suggest that whn expression encompasses the transition from a proliferative to a postmitotic state and that whn regulates the initiation of terminal differentiation.
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PMID:Association between mouse nude gene expression and the initiation of epithelial terminal differentiation. 1019 Oct 51

Three major inhibitors of the NF-kappaB/Rel family of transcription factors, IkappaBalpha, IkappaBbeta, and IkappaBepsilon, have been described. To examine the in vivo role of the most recently discovered member of the IkappaB family, IkappaBepsilon, we generated a null allele of the murine IkappaBepsilon gene by replacement of all coding sequences with nlslacZ. Unlike IkappaBalpha nullizygous mice, mice lacking IkappaBepsilon are viable, fertile, and indistinguishable from wild-type animals in appearance and histology. Analysis of beta-galactosidase expression pattern revealed that IkappaBepsilon is mainly expressed in T cells in the thymus, spleen, and lymph nodes. Flow cytometric analysis of immune cell populations from the bone marrow, thymus, spleen, and lymph nodes did not show any specific differences between the wild-type and the mutant mice, with the exception of a reproducible 50% reduction of the CD44-CD25+ T cell subspecies. The IkappaBepsilon-null mice present constitutive up-regulation of IgM and IgG1 Ig isotypes together with a further increased synthesis of these two isotypes after immunization against T cell-dependent or independent Ags. The failure of observable augmentation of constitutive nuclear NF-kappaB/Rel-binding activity is probably due to compensatory mechanisms involving IkappaBalpha and IkappaBbeta, which are up-regulated in several organs. RNase-mapping analysis indicated that IL-1alpha, IL-1beta, IL-1Ra, and IL-6 mRNA levels are constitutively elevated in thioglycolate-elicited IkappaBepsilon-null macrophages in contrast to GM-CSF, G-CSF, and IFN-gamma, which remain undetectable.
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PMID:IkappaBepsilon-deficient mice: reduction of one T cell precursor subspecies and enhanced Ig isotype switching and cytokine synthesis. 1057 Feb 87

We have determined the expression pattern of the A-raf proto-oncogene in the embryonic and adult mouse. Western blot analysis of protein lysates from tissues of adult mice show that p69A-raf is ubiquitously expressed, but that levels of expression vary among different tissues. To determine the cell-specific expression pattern of A-raf, we generated transgenic mice expressing the beta-galactosidase reporter gene from the A-raf promoter. We show that A-raf expression is highly specific within a given tissue, and we identify cell types expressing this gene in the adult testis, epididymis, vas deferens, seminal vesicle, ovary, oviduct, bladder, kidney, intestine, heart, spleen, thymus, and cerebellum. In the embryo, ubiquitous expression of the reporter gene is observed, but the highest levels of expression are specifically detected in the embryonic heart at stages 9.5-11.5 days post-coitum.
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PMID:Expression of the A-raf proto-oncogene in the normal adult and embryonic mouse. 1076 64

KCNQ1 is the human gene responsible in most cases for the long QT syndrome, a genetic disorder characterized by anomalies in cardiac repolarization leading to arrhythmias and sudden death. KCNQ1 encodes a pore-forming K+ channel subunit termed KvLQT1 which, in association with its regulatory beta-subunit IsK (also called minK), produces the slow component of the delayed-rectifier cardiac K+ current. We used in situ hybridization to localize KvLQT1 and IsK mRNAs in various tissues from adult mice. We showed that KvLQT1 mRNA expression is widely distributed in epithelial tissues, in the absence (small intestine, lung, liver, thymus) or presence (kidney, stomach, exocrine pancreas) of its regulator IsK. In the kidney and the stomach, however, the expression patterns of KvLQT1 and IsK do not coincide. In many tissues, in situ data obtained with the IsK probe coincide with beta-galactosidase expression in IsK-deficient mice in which the bacterial lacZ gene has been substituted for the IsK coding region. Because expression of KvLQT1 in the presence or absence of its regulator generates a K+ current with different biophysical characteristics, the role of KvLQT1 in epithelial cells may vary depending on the expression of its regulator IsK. The high level of KvLQT1 expression in epithelial tissues is consistent with its potential role in K+ secretion and recycling, in maintaining the resting potential, and in regulating Cl- secretion and/or Na+ absorption.
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PMID:Differential expression of KvLQT1 and its regulator IsK in mouse epithelia. 1120 32

The major adrenal steroid dehydroepiandrosterone (DHEA) enhances memory and immune function but has no known dedicated receptor; local metabolism may govern its activity. We described a cytochrome P450 expressed in brain and other tissues, CYP7B, that catalyzes the 7alpha-hydroxylation of oxysterols and 3beta-hydroxysteroids including DHEA. We report here that CYP7B mRNA and 7alpha-hydroxylation activity are widespread in rat tissues. However, steroids related to DHEA are reported to be modified at positions other than 7alpha, exemplified by prominent 6alpha-hydroxylation of 5alpha-androstane-3beta,17beta-diol (A/anediol) in some rodent tissues including brain. To determine whether CYP7B is responsible for these and other activities we disrupted the mouse Cyp7b gene by targeted insertion of an IRES-lacZ reporter cassette, placing reporter enzyme activity (beta-galactosidase) under Cyp7b promoter control. In heterozygous mouse brain, chromogenic detection of reporter activity was strikingly restricted to the dentate gyrus. Staining did not exactly reproduce the in situ hybridization expression pattern; post-transcriptional control is inferred. Lower level staining was detected in cerebellum, liver, and kidney, and which largely paralleled mRNA distribution. Liver and kidney expression was sexually dimorphic. Mice homozygous for the insertion are viable and superficially normal, but ex vivo metabolism of DHEA to 7alpha-hydroxy-DHEA was abolished in brain, spleen, thymus, heart, lung, prostate, uterus, and mammary gland; lower abundance metabolites were also eliminated. 7alpha-Hydroxylation of 25-hydroxycholesterol and related substrates was also abolished, as was presumed 6alpha-hydroxylation of A/anediol. These different enzyme activities therefore derive from the Cyp7b gene. CYP7B is thus a major extrahepatic steroid and oxysterol hydroxylase and provides the predominant route for local metabolism of DHEA and related molecules in brain and other tissues.
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PMID:Neurosteroid hydroxylase CYP7B: vivid reporter activity in dentate gyrus of gene-targeted mice and abolition of a widespread pathway of steroid and oxysterol hydroxylation. 1129 Jul 41

A biotin-streptavidin system was established to directly visualize infectious bursal disease virus (IBDV)-binding cells in cell culture or in fresh tissues. The cells or tissue sections were first incubated with a biotinylated, purified IBDV strain GZ911 and then with a streptavidin-beta-galactosidase conjugate. In the presence of the enzyme substrate X-gal, IBDV-binding cells were labeled in blue color. By applying this method to frozen tissue sections, virus-binding sites were localized in situ in the bursa, spleen, and kidney tissue sections, whereas no positive cells were detected in the thymus tissue sections. Chicken embryo fibroblasts, Vero cells, MOP-8 cells, 293-EBNA cells, PANC-1 cells, and HuTu 80 cells were found to bind to the virus. However, the binding of the virus to MDA-MB-231 cells and SVG p12 cells was undetectable. This method can be employed for the expressional cloning of IBDV receptor and can be applied to studies on other avian viruses.
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PMID:In situ localization of infectious bursal disease virus-binding cells by a biotin-streptavidin system. 1141 36

Gene transfer of reporter genes may trigger immune responses against the heterologous protein resulting in shortening of gene expression and inflammation. We generated transgenic rats expressing the lacZ gene under the control of the human immunodeficiency virus type 1 (HIV-1) long-terminal repeat (LTR) (HIV-lacZ) to obtain rats with undetectable transgene expression using histologic methods, thus avoiding interference with beta-galactosidase (beta-gal) expression from gene transfer, and displaying immune tolerance toward beta-gal. LacZ transgenic mice with tolerance toward beta-gal have already been used for gene transfer but rats constitute unique animal models with several advantages compared to mice. Two transgenic lines displayed low levels of beta-gal mRNA in most organs tested, as detected only by reverse transcription-polymerase chain reaction (RT-PCR). The protein was undetectable by immunohistology and was only detected in the thymus and spleen using a sensitive enzyme-linked immunosorbent assay (ELISA). HIV-lacZ transgenic rats displayed immune tolerance to beta-gal because immunization with beta-gal resulted in markedly lower cellular and antibody responses compared to wild-type controls, whereas immunization with a nonrelated antigen, keyhole limpet hemocyanin (KLH), resulted in comparable immune responses. The usefulness of this model in gene transfer was tested using a retroviral vector, which does not elicit destructive immune responses against transduced cells. Retroviral-mediated nlslacZ gene transfer in the liver resulted in nuclear beta-gal expression for longer than 12 months in HIV-lacZ transgenic rats, whereas wild-type controls showed nuclear beta-gal expression for less than 1 month. After gene transfer of nlslacZ to the liver, antibodies, cytotoxic T lymphocytes (CTLs), and proliferation against beta-gal were detected in wild-type controls but not in HIV-lacZ transgenic rats. In conclusion, HIV-lacZ transgenic rats displaying low beta-gal expression and immune tolerance toward beta-gal are a useful tool to analyze the spatial and temporal expression of the beta-gal protein in gene transfer experiments using lacZ as a reporter gene.
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PMID:lacZ transgenic rats tolerant for beta-galactosidase: recipients for gene transfer studies using lacZ as a reporter gene. 1216 20

CSF-1 stimulates monocyte and osteoclast populations. However, the molecular mechanisms involved in regulating CSF-1 gene expression are unclear. To identify regulatory regions that control normal CSF-1 gene expression, a -774/+183-bp fragment of the murine CSF-1 promoter was analyzed in vitro and in vivo. Transcriptional activity was high in cultured osteoblasts that express CSF-1 mRNA compared to ARH-77 B cells that lack CSF-1 gene expression. Transient transfection of osteoblasts with promoter deletion constructs showed that the -774-bp fragment conferred the highest transcriptional activity and contained activator and repressor sequences. To assess the ability of the CSF-1 promoter to confer normal tissue expression of CSF-1, transgenic mice containing the -774/+183-bp region driving the E. coli beta-galactosidase (lacZ) reporter gene were generated. beta-Gal analysis of whole tissue extracts showed transgene expression in all tissues tested except liver and kidney. At the cellular level, the pattern of beta-gal expression in the spleen, thymus, bone, lung, and testes of adult transgenic mice mimicked normal endogenous CSF-1 mRNA expression in non-transgenic littermates detected by in situ hybridization. This region also directed appropriate transgene expression to sites in other tissues known to synthesize CSF-1, with the exception of the liver and kidney. These findings indicate that the -774-bp fragment contains cis-acting elements sufficient to direct CSF-1 gene expression in many tissues. CSF-1 promoter/lacZ mice may be useful for studying the transcriptional mechanisms involved in regulating CSF-1 gene expression in tissues throughout development.
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PMID:Analysis of the mouse CSF-1 gene promoter in a transgenic mouse model. 1281 Aug 44

Six genes are widely expressed during vertebrate embryogenesis, suggesting that they are implicated in diverse differentiation processes. To determine the functions of the Six1 gene, we constructed Six1-deficient mice by replacing its first exon by the beta-galactosidase gene. We have previously shown that mice lacking Six1 die at birth due to thoracic skeletal defects and severe muscle hypoplasia affecting most of the body muscles. Here, we report that Six1(-/-) neonates also lack a kidney and thymus, as well as displaying a strong disorganisation of craniofacial structures, namely the inner ear, the nasal cavity, the craniofacial skeleton, and the lacrimal and parotid glands. These organ defects can be correlated with Six1 expression in the embryonic primordium structures as revealed by X-Gal staining at different stages of embryogenesis. Thus, the fetal abnormalities of Six1(-/-) mice appear to result from the absence of the Six 1 homeoprotein during early stages of organogenesis. Interestingly, these Six1 defects are very similar to phenotypes caused by mutations of Eya 1, which are responsible for the BOR syndrome in humans. Close comparison of Six1 and Eya 1 deficient mice strongly suggests a functional link between these two factors. Pax gene mutations also lead to comparable phenotypes, suggesting that a regulatory network including the Pax, Six and Eya genes is required for several types of organogenesis in mammals.
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PMID:Thymus, kidney and craniofacial abnormalities in Six 1 deficient mice. 1283 66

The thymus expresses proinsulin, among many other tissue-specific antigens, and the inheritance of genetically determined low thymic proinsulin expression has been associated with impaired proinsulin-specific autoreactive T-cell tolerance and type 1 diabetes susceptibility. The cellular and molecular biology of proinsulin expression in the thymus remains unknown, and contradictory reports exist regarding the identity of proinsulin-producing cells. Using knock-in mice expressing beta-galactosidase (beta-Gal) under the control of an endogenous insulin promoter, we found that thymic proinsulin and beta-Gal transcripts were detectable at high levels in purified thymic epithelial cells. Immunohistochemical analysis of beta-Gal activity showed that most proinsulin expression can be accounted for by rare medullary epithelial cells of the Hassall's corpuscles. Moreover, flow cytometry analyses of beta-Gal-positive cells showed that only 1-3% of all epithelial cells express proinsulin, and this technique will now provide us with a method for isolating the proinsulin-producing cells in mouse thymus.
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PMID:Proinsulin expression by Hassall's corpuscles in the mouse thymus. 1474 85


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