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At least 19 recordsLinked to original sources
PubMed1991

Tissue-specific and non-tissue-specific heavy-chain isoforms of myosin in the brain as revealed by monoclonal antibodies.

Four types of monoclonal antibody (BM-1, BM-2, BM-3 and BM-4) each having distinctive tissue specificity were obtained by immunizing mice with purified bovine cerebrum myosin. Both BM-1 and BM-2 reacted most efficiently with cerebrum myosin and less efficiently with myosins from other limited nonmuscle tissues, the tissue specificity of BM-1 being much narrower than that of BM-2. BM-3 reacted more efficiently with several other nonmuscle myosins than with cerebellar or cerebral myosin. BM-4 recognized various nonmuscle and smooth muscle myosins with a nearly equal efficiency. Cerebral myosin as well a cerebellar myosin contained two or more electrophoretic variants of the heavy chains. BM-1 and BM-3 as well as BM-2 and BM-3 were found to recognize selectively these distinct heavy-chain isoforms. The antigenic sites of the three tissue-specific antibodies (BM-1, BM-2 and BM-3) were all localized near the head/tail junction of the myosin molecules, while that of non-tissue-specific antibody BM-4 was near the center of the tail. These and additional results indicate that mammalian brain tissues as well as several other nonmuscle tissues contain multiple heavy-chain isoforms of myosin, the levels of which differed considerably from one tissue to another.

Animals↗
PubMed1991

Characterization of muscle and non muscle Xenopus laevis tropomyosin mRNAs transcribed from the same gene. Developmental and tissue-specific expression.

We have isolated and characterized three Xenopus laevis tropomyosin cDNAs (XTM alpha 2, XTM alpha 4 and XTM05). XTM alpha 2 and XTM alpha 4 were isolated from a stage-42 embryo cDNA library and XTM05 from an oocyte cDNA library. XTM alpha 2 and XTM alpha 4 both code for a 284-amino-acid protein homologous to the skeletal alpha tropomyosin but diverge in their 3' untranslated sequences. This divergence is due to an absence of splicing in the early embryo. XTM05 codes for a 248-amino-acid non-muscle tropomyosin. Sequence analysis indicates that the three cDNAs are generated from a single gene which uses two promoters and possibly three sets of alternate exons. Northern blot analysis, with specific probes against each cDNA, was used to study the expression of the X. laevis alpha tropomyosin gene during development and in specific tissues. This analysis showed a different temporal usage of the two promoters and characterized the tissue-specific expression of the different transcripts.

Amino Acid Sequence↗
PubMed1978

[Tissue-specific inhibition of DNA synthesis by contactins, factors that possess tissue-specific adhesive activity].

Highly purified factors extracted from the liver and lungs of adult rats, tissue-specifically increasing the stability of intercellular contacts and of cell plasma membranes to mechanical disruption, were found to decrease, in the same manner, the labeling index (LI) in explants of the embryonic tissue of mice. The comparison of the action of these factors on the LI, and on mechanical properties of the tissue has shown that the latter effect is manifested earlier than the former one.

Adhesiveness↗
PubMed1992

Tissue-specific nutritional regulation of angiotensinogen in adipose tissue.

Recent studies have found that angiotensinogen is expressed in white and brown fat pads, and adipocytes have been implicated as a primary source of angiotensinogen in several other tissues. The functional significance of this unexpected expression is unknown. To address this, we studied angiotensinogen messenger RNA (mRNA) expression and angiotensinogen secretion in adipose tissue and isolated adipocytes comparing fasted and refed rodents and those with genetic obesity with normal controls. Control 2-month-old Sprague-Dawley rats, those fasted for 3 days, or those fasted for 2 days and refed for 6 days were killed, and adipocytes were isolated from epididymal fat pads using collagenase digestion. Angiotensinogen mRNA was reduced to 14.6 +/- 2.3% of control levels under fasted conditions and increased to 228 +/- 53% of control levels after refeeding. Angiotensinogen release from adipocytes was reduced to 33% of control levels by fasting and increased to 183% by refeeding. These effects of fasting and refeeding on angiotensinogen regulation were tissue specific since liver angiotensinogen mRNA and serum angiotensinogen concentrations were unaffected. Systolic blood pressure, however, was modulated by fasting and refeeding in a manner parallel to adipocyte angiotensinogen expression. In related experiments, angiotensinogen secretion per epididymal fat pad of the ob/ob mouse model of obesity was increased an average of 3.4-fold compared with control. We conclude angiotensinogen expression in white adipocytes is regulated nutritionally in a tissue-specific manner. We propose that adipocyte angiotensinogen could play a previously unrecognized role in regulating adipose tissue blood supply and thereby fatty acid efflux from fat.(ABSTRACT TRUNCATED AT 250 WORDS)

Adipose Tissue↗
PubMed1991

A quantitative genetic analysis of tissue-specific catalase activity in Mus musculus.

Tissue-specific catalase activity in 3-week-old animals from inbred mouse strains 129/ReJ, BALB/c, C3H/HeAnl/Cas-1b, C3H/HeSnJ, C3H/S, C57BL/6J, and Swiss-Webster was found to be highly variable by analysis of variance (P = 0.01). Appropriate crosses were made among strains which were classified as normal (BALB/c, C3H/HeSnJ, C3H/S), hypocatalasemic (129/ReJ, C57BL/6J), and acatalasemic (C3H/HeAnl/Cas-1b) with respect to blood catalase activity to study the inheritance of the blood, kidney, liver, and lung catalase activity levels in a number of generations (reciprocal F1's, F2, two backcrosses--BC1 and BC2--and some RI lines). Segregation analysis and statistical methods which tested different models of inheritance as well as calculations of heritability were used in an effort to assess and evaluate genetic parameters that affect catalase activity. Results indicate that the inheritance of blood catalase activity in the cross involving acatalasemic and normal (BALB/c, C3H/HeSnJ) strains is compatible with the single-locus difference between the parental strains; however, the difference between the acatalasemic and the hypocatalasemic strain (C57BL/6J) would require additional genetic interaction for a satisfactory explanation. A similar pattern of generalization also applies to the inheritance of kidney catalase activity. The segregation pattern for the liver and lung catalase activity in most crosses is significantly different from the expectations of the single locus model. These results are compatible with the concept that a number of genes must affect tissue-specific catalase activity in mice. These may include previously described (e.g., Ce-1 and Ce-2) or novel genetic regulators/modifiers which interact with a single structural gene (Cas-1) or its product to produce the catalase phenotype characteristic of specific tissues in each strain.

Acatalasia↗
PubMed1992

Immune response: tissue specific T-lymphocytes.

The lymphatic system forms a 'blind' plexus of vessels that in general are found in tissue which has an inherently high replicative capacity. It is this system that is responsible for the rapid deployment and circulation of tissue-specific T-lymphocytes for the inspection of cell-surface aberrations within the tissue. The presence of tissue-specific T-lymphocytes explains why 90% of lymphocytes are found outside the lymphatic system and why they migrate in a selective manner. The tissue-specific T-lymphocyte is considered to express a common lymphocyte cell surface pattern, the homotype, and a tissue-specific cell-surface pattern, the histotype which may involve MHCA and mHCA. It is the histotypic pattern that is responsible for the tissue specificity of the tissue-specific T-lymphocyte. The presence of tissue-specific T-lymphocytes does pose problems for the immune system. If different tissue-specific T-lymphocytes met within a particular tissue, 'lost' lymphocytes, an immune response will be generated against the intruder (lost lymphocyte), and the intruder will not be able to recruit other immunocompetent cells in that tissue. This immune reaction is an attempt to change the histotypic pattern of the intruder. This situation would explain the autologous immune response. This response however is suppressed in the systemic system by immunosuppressive compounds from the liver. It is only in the tissues that the tissue-specific T-lymphocytes are released from this suppression, in order to initiate immune reactions against aberrant cell-surface patterns.

Animals↗
PubMed1992

Role of local environmental factors in determining tissue-specific effects of estrogen: examination of uterine tissues transplanted to brain.

Estrogen stimulates uterine epithelial cells to divide, but not estrogen-concentrating neurons in the adult brain. This effect correlates with recent evidence that estrogen can induce the expression of certain growth-related genes in uterus which are not directly induced by estrogen in the adult brain. The possibility that local diffusible factors play a major role in determining tissue-specific effects of estrogen was examined by transplanting uterine tissues into the brain, muscle and kidney of adult rats and then comparing the effects of estrogen on the incorporation of [3H]thymidine and the expression of Fos-, cdc2- and Rb-like immunoreactivity (IR) on native and transplanted uterine tissues, as well as in estrogen-concentrating regions of the brain adjacent to the uterine grafts. In native uteri, estrogen treatment stimulated Fos-, cdc2-, and Rb-like IR, as well as [3H]thymidine incorporation, within lumenal and glandular epithelial cells. All of these effects were estrogen responsive--no immunoreactive staining within uterine epithelial cells and no signs of epithelial cell proliferation were observed in the native uteri of non-estrogen-treated animals. When uterine tissues were transplanted to brain, Fos-, cdc2-, and Rb-like IR epithelial cells, as well as many [3H]thymidine-incorporating uterine epithelial cells, were observed in all estrogen-treated animals and in some non-estrogen-treated animals as well. Identical results were obtained when uterine tissues were transplanted to skeletal muscle, but not to kidney (in the kidney, transplanted epithelial cells expressed all four parameters but only in estrogen-treated animals, comparable to the native uterus). In contrast, estrogen did not stimulate cell division and did not induce Fos-, cdc2-, or Rb-like IR within estrogen-concentrating neuronal regions of the ventromedial hypothalamus. In addition, the presence of uterine tissue in the brain did not confer the ability of estrogen to stimulate any of these parameters within nearby, estrogen-concentrating regions. These data suggest that there are factors in brain and muscle which can allow uterine epithelial cells to divide in the absence of estrogen. There was no evidence of a diffusible factor in brain which inhibits uterine epithelial cell division, nor of a diffusible factor in uterus which can confer estrogenic stimulation of growth-related genes and cell division to central nervous system neurons. In addition, the data provide the first evidence for estrogen regulation of cdc2 and Rb expression in normal uterus.

Animals↗
PubMed1992

Tissue-specific expression of the mouse alpha 2(I) collagen promoter. Studies in transgenic mice and in tissue culture cells.

We sought to determine the cis-acting elements responsible for the pattern of tissue specific expression of the mouse alpha 2(I) collagen gene. Using an RNase protection assay we first verified that expression of the alpha 2(I) collagen gene is mainly confined to tendons, bone, and skin in mice. Both transgenic mice and DNA transfection of tissue culture cells were used as experimental approaches. Transgenic mice lines were generated harboring chloramphenicol acetyltransferase (CAT) chimeric genes that contained either (a) 2000 base pairs (bp) of 5'-flanking sequences of the mouse alpha 2(I) collagen gene plus additional sequences between +418 and +1524 of the first intron of this gene or (b) the same promoter sequences without intron sequences or (c) the 350-bp proximal promoter sequences. Transgenic mice containing both types of 2000-bp promoters showed a pattern of CAT expression that was tissue specific. The presence of sequences of the first intron in the transgene did not increase the level of promoter activity. Transgenic mice harboring the 350-bp alpha 2(I) collagen promoter also showed a pattern that was tissue-specific except that high level expression also occurred in the brain. This suggests that negative regulation is an important component of tissue-specific expression. In order to analyze the first 350 bases in detail, we performed transient expression experiments, using promoter fragments attached to the luciferase reporter gene. Fibroblasts, which show a high level expression of the endogenous alpha 2(I) collagen gene, and B cells, in which the gene is silent, were transfected with a series of deletions and substitution mutations within the proximal 350-bp promoter. These experiments were unable to define unique cell-specific cis-acting elements. However, when the sequence between -315 and -284 was tandemly repeated upstream of a minimal alpha 2(I) collagen promoter (-41 to +54), the activity of this construction was considerably higher in fibroblasts than in B cells when compared with the minimal promoter itself. In gel retardation assays, the levels of complexes that bind to this sequence were higher in fibroblast nuclear extracts than in myeloma nuclear extracts. Our results are consistent with the hypothesis that the -315 to -284 DNA sequence participates in the cell-specific control of the alpha 2(I) collagen gene in fibroblasts.

Animals↗
PubMed1991

Species-specific differences in tissue-specific expression of alcohol dehydrogenase are under the control of complex cis-acting loci: evidence from Drosophila hybrids.

Differences in the expression of alcohol dehydrogenase in the hindgut and testis of adult Drosophila virilis, D. texana, D. novamexicana and D. borealis flies were observed. These heritable differences do not arise due to chromosomal rearrangements, since the polytene chromosome banding patterns did not reveal any such gross chromosomal rearrangements near the Adh locus in any of the tested species. Analysis of the interspecific hybrids revealed that these differences are controlled by complex cis-acting genetic loci. Further, the cis-acting locus controlling the expression of ADH in testis was found to be separable by crossing-over.

Alcohol Dehydrogenase↗
PubMed1992

A polymorphic human kidney-specific non-MHC alloantigen. Its possible role in tissue-specific allograft immunity.

Tissue specific non-MHC alloantigens play a crucial role in allograft immunity. However, their structural properties have remained elusive, largely due to their inability to induce a strong antibody response. We report the characterization of a monkey heteroantiserum, MHK-I, raised against human kidney cells, that serologically reacts specifically with kidney cells after extensive absorptions of anti-HLA class I and II reactivities. The non-MHC MHK-I-binding molecule(s) is expressed only in the renal cortex on the glomerulus, peritubular capillaries, venous endothelium, and tubular epithelium. Immunochemically, MHK-I recognizes a kidney-specific non-MHC alloantigen of Mr 90,000 to 100,000 (90 kD). These properties of MHK-I are similar to those of the previously characterized alloantibodies eluted from rejected kidneys. These alloantibodies bind to the kidney from which the antibody was eluted and to a few others but are unlike MHK-I, which binds to extracts prepared from all human kidneys. Biochemical analysis by two-dimensional electrophoresis (pI ranging between 4.5 and 5.5) and peptide fingerprinting provide further evidence that the alloantigen is polymorphic. These findings imply that the non-MHC kidney-specific molecule(s) may function as target(s) for immune destruction of renal allografts.

Animals↗
PubMed1975

[Tissue-specific depression of DNA synthesis by calcium salt-free liver and lung extracts that are able to increase the stability of cell linkage in the tissue].

The macromolecular fraction of Ca-free salt extracts (Ca-FSE) removed from lungs and liver of adult rats, mice and fishes inhibits DNA synthesis in the embryonic tissue. The effect of Ca-FSE is tissue-specific rather than species-specific. Ca-FSE was earlier reported to increase with the same specificity the tissue stability to mechanical disruption. A concept is proposed that the tissue-specific adhesive factor may play the role of G1-chalone in epithelial tissue.

Animals↗
PubMed2026

Changes in the transcriptome and synthetic lethal dependencies following KRAS mutant expression reveal profound tissue specificity.

Oncogenic KRAS mutations exhibit a striking tissue-restricted tropism, occurring with high frequency in pancreatic, colorectal, and lung adenocarcinomas while remaining rare in other lineages. The molecular basis for why these specific tissues are uniquely permissive to KRAS transformation, and how this context shapes therapeutic vulnerabilities, remains poorly defined. Here, we utilized CRISPR-mediated genome engineering to generate endogenous, conditional KRAS-mutant isogenic cell line models across three primary permissive lineages (lung, colon, and pancreas) and the nonpermissive breast lineage. Integrated genome-wide CRISPR fitness screens and comparative transcriptome analyses revealed that KRAS-driven synthetic lethal (SL) dependencies are profoundly shaped by their tissue of origin. Strikingly, we observed minimal overlap in SL hits across lineages, with only three genes shared among the permissive lines, suggesting that the KRAS oncogene operates through divergent, context-specific genetic networks. Mechanistically, we show that KRAS activation induces a universal MYC-driven metabolic signature, but the specific machinery required to sustain this state is lineage-restricted. We identified a dependency on the diphthamide synthesis pathway to maintain translational fidelity amid a KRAS-induced hypertranslational state. These findings demonstrate that even when driven by the same oncogene, tumors exhibit distinct regulatory landscapes and unique genetic vulnerabilities. Our results provide a framework for developing lineage-aware therapeutic strategies, moving beyond universal KRAS inhibition toward targeted interventions tailored to a tumor's specific tissue context.

Proto-Oncogene Proteins p21(ras)↗
PubMed1992

The binding site of a steroid hormone receptor-like protein within the Drosophila Adh adult enhancer is required for high levels of tissue-specific alcohol dehydrogenase expression.

Developmental and tissue-specific transcription from the Adh distal promoter is regulated in part by the Adh adult enhancer, located 450 to 600 bp upstream from the distal RNA start site. We have characterized four proteins (DEP1 to DEP4), present in Drosophila tissue culture cell nuclear extracts, which bind to this enhancer. DEP1 and DEP2 bind to a positive cis-acting element (-492 to -481) and share nucleotide contacts. A small linker replacement deletion mutation, which disrupts the overlapping DEP1- and DEP2-binding sites, reduces Adh distal transcription in an alcohol dehydrogenase (ADH)-expressing cultured cell line, in the adult fat body (the major tissue of ADH expression), as well as in some but not all adult tissues where ADH is normally expressed. This enhancer element contains an imperfect palindromic sequence similar to steroid hormone receptor superfamily response elements. Binding-site screening of a lambda gt11 expression library has identified the steroid receptor superfamily member fushi tarazu factor 1 (FTZ-F1) as a protein that binds to this site. Anti-FTZ-F1 antibodies have identified DEP1 as FTZ-F1. DEP2 also binds to the FTZ-F1 site from the fushi tarazu zebra element, suggesting that DEP2 may also be a steroid receptor superfamily member. Our results raise the possibility that Adh regulation in certain adult tissues involves a hormone-mediated pathway. Because DEP1 (FTZ-F1) and DEP2 contact some of the same nucleotides within the positive cis element, it is unlikely that they can bind simultaneously. Such alternative binding may play a role in the tissue-specific and developmental transcription of Adh.

Alcohol Dehydrogenase↗
PubMed2026

Predictive design of tissue-specific mammalian enhancers that function in the mouse embryo.

Enhancers control tissue-specific gene expression across animals1. Although deep learning2,3 has enabled enhancer prediction and design in mammalian cell lines and non-mammalian model organisms4-10 (reviewed in a previous publication11), it remains unclear whether such approaches can operate within the regulatory complexity of mammalian genomes and tissues in vivo. Here we present a general strategy for designing tissue-specific enhancers that function reliably in mice. We use deep learning to train compact convolutional neural networks on curated chromatin accessibility data and fine-tune them by transfer learning on validated human and mouse enhancers. Guided by these models, we design 15 synthetic enhancers for the heart, limb and central nervous system in mouse embryos, all of which are active in their intended target tissue. These results demonstrate that mammalian enhancer function can be reliably inferred from DNA sequence alone, enabling the predictive de novo design of tissue-specific synthetic enhancers from modest training sets. This work establishes a generalizable framework for programmable control of mammalian gene expression in vivo, opening new avenues in functional genomics, synthetic biology and gene therapy.

Animals↗
PubMed1975

Conversion of human erythrocyte-adenosine deaminase activity to different tissue-specific isozymes. Evidence for a common catalytic unit.

Adenosine deaminase activity resides in various characteristic isozymes in red blood cells (RBC-ADA) and other tissues. Absence of RBC-ADA has been reported in a proportion of patients with autosomally inherited severe combined immunodeficiency (SCID). We have previously reported that the tissue isozymes of ADA are also deficient in children with SCID and RBC-ADA deficiency, although these isozymes differ from RBC-ADA in molecular weight, accessible SH groups, and electrophoretic mobility. The deficiency of all types of ADA in SCID implies that a catalytic unit of ADA in each isozyme is coded by the same structural gene. The relationship of RBC-ADA and the different tissue ADA isozymes is the subject of this paper. Incubation of RBC-ADA with ADA-deficient liver, kidney, and fibroblast extracts resulted in the appearance of new isozymes of ADA. These newly generated isozymes had the physicochemical and electrophoretic characteristics of the tissue-specific isozymes obtained from normal tissues. The electrophoretic mobility of the isozyme generated appeared to depend upon the tissue utilized and corresponded to the electrophoretic mobilities of the ADA isozymes found naturally in each of the different tissues. Additionally, the genetically determined polymorphism exhibited by RBC-ADA could be detected in the isozyme generated. Incubation with normal kidney also caused conversion of the RBC isozyme to the kidney form. These findings further support the concept that the catalytic activity of each of the several forms of the ADA enzyme resides in a single molecule coded at the same genetic locus as is defective in one form of SCID. The tissue-specific isozymes, which differ in electrophoretic mobility and molecular weight, are generated by interaction of the RBC catalytic unit with tissue-specific factors present in the different tissues of normal humans and patients.

Aminohydrolases↗