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Query: EC:3.4.23.15 (renin)
 35,795 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In a survey of inbred and wild mouse DNAs for genetic variation at the duplicate renin loci, Ren-1 and Ren-2, a variant Not I hybridization pattern was observed in the wild mouse M. hortulanus. To determine the basis for this variation, the structure of the M. hortulanus renin loci has been examined in detail and compared to that of the inbred strain DBA/2. Overall, the gross features of structure in this chromosomal region are conserved in both Mus species. In particular, the sequence at the recombination site between the linked Ren-1 and Ren-2 loci was found to be identical in both DBA/2 and M. hortulanus, indicating that the renin gene duplication occurred prior to the divergence of ancestors of these mice. Renin flanking sequences in M. hortulanus, however, were found to lack four DNA insertions totaling approximately 10.5 kb which reside near the DBA/2 loci. The postduplication evolution of the mouse renin genes is thus characterized by a number of insertion and/or deletion events within nearby flanking sequences. Analysis of renin expression showed little or no difference between these mice in steady state renin RNA levels in most tissues examined, suggesting that these insertions do not influence expression at those sites. A notable exception is the adrenal gland, in which DBA/2 and M. hortulanus mice exhibit different patterns of developmentally regulated renin expression.
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PMID:DNA insertions distinguish the duplicated renin genes of DBA/2 and M. hortulanus mice. 131 69

Certain mouse strains (e.g., DBA/2) contain two renin genes (termed Ren-1 and Ren-2) and express higher renin levels in nonkidney tissues than strains with a single renin gene. The 5'-flanking regions of the Ren-1 and Ren-2 genes contain several TATA boxes preceding putative transcriptional start sites. These initiators are termed P1a, P1, P2 (from 5' to 3'), and their function (with the exception of P2) is largely unknown. In this study, we mapped the renin transcriptional start sites in renal and extrarenal tissues [adrenal, brain, testis, heart, and submandibular gland (SMG)] and examined the effect of adenosine 3',5'-cyclic monophosphate (cAMP) on tissue specific promoter usage. Our results showed that, in the unstimulated state, P2 (the predicted initiator) is active in all DBA/2 mouse tissues. Additional transcriptional start sites were detected in the adrenal and testis (originated by P1a and P2) and the SMG (originated by P1a, P1, and P2). The administration of 8-bromoadenosine 3',5'-cyclic monophosphate led to selective stimulation of P1a in the adrenal but did not affect the selective usage of initiation sites in other organs. A locus-specific ddNTP primer extension assay was used to verify which renin gene is induced by cAMP. Results indicated that both Ren-1 and Ren-2 responded to cAMP treatment in identical fashion. Taken together, these data indicate that more than one form of renin transcript is present in several mouse tissues. There is tissue specificity in promoter usage in the unstimulated state and in response to cAMP.
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PMID:Tissue specificity of renin promoter activity and regulation in mice. 131 8

In the DBA/2 mouse submandibular gland (SMG), renin is predominantly the expression product of the renin gene Ren-2d. Prorenin is synthesized and rapidly converted to a constitutively secreted single-chain intermediate, which is then processed to and stored as the mature two-chain (2C) form, which is released by regulated secretion. To evaluate whether the mode of renin processing is cell dependent, renin (Ren-2d) complementary DNA was stably integrated in the genome of Chinese hamster ovary (CHO) cells and a mouse pituitary cell line (AtT-20) by transfection, and renin processing and secretion were examined. Transfected CHO cells secreted exclusively prorenin, whereas transfected AtT-20 cells secreted both prorenin and active renin. AtT-20 cells processed prorenin to the single-chain polypeptide (1C-renin) that was the main storage form and was not further processed to the 2C form of correct size, whose site of generation or function is uncertain at this time. In addition, the conversion of prorenin to 1C-renin was much slower in AtT-20 cells than in the SMG. Thus the patterns of renin biosynthesis and secretion in AtT-20 cells show major differences when compared with these processes in the native SMG, suggesting that cell-dependent characteristics, e.g., the presence of specific processing enzymes, are important factors influencing mouse renin processing.
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PMID:Cell-dependent posttranslational processing and secretion of recombinant mouse renin-2. 153 49

Many inbred strains of mice have a single locus encoding renin, Ren-1, whereas other inbred strains have two tandemly linked loci, Ren-1 and Ren-2. Each of these renin genes in inbred mice exhibits a unique pattern of tissue-specific expression. As a prerequisite to understanding the structural basis for the expression differences, we have physically characterized the sequence organization of this chromosomal region in both types of strains. Pulsed field gel electrophoresis was initially used to compare the long-range structure of this region in C57BL/6 (Ren-1) and DBA/2 (Ren-1 + Ren-2) mice. The structure in both inbred strains is extremely similar, except for an additional 30 kb containing Ren-2 in DBA/2 mice. The boundaries of the extra 30-kb segment were sequenced and compared to homologous sequences flanking the Ren-1 alleles. This analysis identified the precise recombination site, and also the presence of a large insertion, between the renin loci in DBA/2. The renin gene duplication apparently resulted from recombination between sequences sharing little homology, suggesting that nonhomologous chromosomal breakage and rejoining may have been involved mechanistically in the event.
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PMID:Physical characterization of genetic rearrangements at the mouse renin loci. 215 28

A renin promoter-large tumor antigen (T antigen) fusion gene was constructed to provide a reporter function for renin expression in transgenic mice. These transgenic mice gave rise to tumors in subcutaneous soft tissue, which was attributed to transgene expression at this site. An immunohistochemical analysis of transgenic fetuses from several independent lines revealed scattered T-antigen-containing mesenchymal cells and fibroblasts in the subcutaneous layer of the skin between the panniculus carnosus muscle of the skin and the skeletal muscle of the body wall. This localization is consistent with the location of overt tumorigenesis in adult mice. This pattern was specific for the renin-T antigen fusion gene as no immunohistochemical staining was observed in transgenic fetuses containing a heterologous promoter-T antigen fusion gene. Northern blot analysis of tumor RNA indicated that most of the tumors expressed both T antigen and the endogenous renin gene Ren-1c. In addition, when multiple renin genes were introduced by crossing transgenic mice with nontransgenic DBA/2J mice, which contain another allele of the Ren-1 locus as well as the duplicated locus Ren-2, the resultant tumors expressed the Ren-2 gene. Northern blots were then used to analyze renin expression in the subcutaneous tissue of normal mice. Fully processed renin mRNA was detected in eviscerated 15.5-day postcoitus fetal and newborn carcasses and in newborn skin. Our data indicate that there is a renin-expressing cell population in fetal and newborn subcutaneous tissue.
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PMID:Expression of murine renin genes in subcutaneous connective tissue. 217 70

To characterize further the tissue-specific control of the mouse Ren-2 gene, and in particular its expression in the adrenal gland, we have introduced the DBA/2 Ren-2 gene into the genome of Ren-1c/Ren-1c mice. Here we report our observations on Ren-2 transgenic mice. Expression was found in the correct spectrum of tissues and included appropriate hormonal control in the submandibular gland. Quantitatively transcript levels varied both positively (adrenal gland and sex-accessory tissue) and negatively (submandibular gland and kidney) with respect to normal Ren-2 expression. In the DBA/2 inbred mouse strain expression in the female adrenal gland cycles during oestrus between the X-zone and the zona fasciculata. Transgene expression within the adrenal gland was restricted to the X-zone. Therefore this phenotype, which is characteristic of most two-renin-gene strains of mice, contrasts with that found in the strain DBA/2 from which the transgene was derived. This suggests that cell-specific expression in the DBA/2 adrenal gland is mediated in trans by at least one additional locus. We demonstrate that suitable genetic crosses of the transgenic mice can partially restore the cycling phenotype.
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PMID:Expression of the DBA/2J Ren-2 gene in the adrenal gland of transgenic mice. 248 Feb 33

To investigate the ontogeny of the renin-angiotensin system we studied the characteristics and location of angiotensin II (AII) receptors in mouse fetuses and examined sites of renin mRNA expression by in situ hybridization and Northern blot analysis. Autoradiographic analysis of the binding of 125I-[Sar1,Ala8]AII to slide-mounted frozen sections of 17-day-old DBA/2N mice revealed abundant AII receptors widely distributed throughout the body. High receptor density was found in primitive mesenchymal tissue under the epidermis and surrounding muscle and cartilage, in skeletal and smooth muscle, and in all layers of the adrenal cortex. Lower receptor density was seen in the kidney, liver, and lungs. The autoradiographic staining was abolished by incubation of the sections with excess unlabeled AII. Scatchard analysis of the binding of 125I-[Sar1,Ala8,]AII to membrane-rich fractions of eviscerated fetuses showed a single type of high affinity receptors with a Kd of 2.9 x 10(-9) M and a receptor concentration of 3300 fmol/mg protein. Localization of renin mRNA was analyzed by in situ hybridization using an antisense 35S-labeled riboprobe transcribed from a mouse renin2 cDNA clone. Hybridization to fetal tissue sections showed high intensity staining in the kidney and adrenal cortex. Northern blot analysis confirmed the high expression of renin mRNA in the fetal kidney. The presence of an active renin-angiotensin system in the fetus was confirmed by the demonstration of renin-like activity and bioactive AII in fetal extracts. The widespread distribution of AII receptors in the fetus, compared to the discrete localization to specialized tissues in the adult, may indicate a unique role for the peptide during development.
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PMID:Distribution of angiotensin II receptors and renin in the mouse fetus. 264 65

The renin-encoding genes have been cloned from high (Ren-1d, Ren-2d)- and low (Ren-1c)-renin-producing strains of mice (DBA/2J and C57BL/10). Each of the genes is approx. 9.6 kb in length and consists of nine exons and eight introns. The entire nucleotide sequence of the Ren-1d gene has been determined and the 5'-flanking regions of the three genes, Ren-1c, Ren-1d and Ren-2d, have been compared. The significance of several potential regulatory signals found in the DNA is discussed.
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PMID:The nucleotide sequence of a mouse renin-encoding gene, Ren-1d, and its upstream region. 269 39

In addition to the Ren-1 gene common to all mice, some inbred strains carry a second copy of the renin structural gene, Ren-2. These two loci are tightly linked genetically on mouse chromosome one. We have used pulsed field gel electrophoresis (PFGE) to study the physical arrangement of the two renin genes in the inbred strain DBA/2. PFGE mapping permitted the construction of a restriction map of the Ren loci spanning roughly 120 Kb. The results indicate that the genes are transcribed in the same relative direction, that Ren-2 lies upstream relative to Ren-1, and that the respective coding sequences are separated by approximately 20 Kb.
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PMID:Close physical linkage of the murine Ren-1 and Ren-2 loci. 283 27

We report the molecular cloning of cDNA copies of DBA/2 mouse submaxillary gland (SMG) renin mRNA, which were used to probe Southern transfers of mouse genomic DNA. The results suggested either that there is a single renin gene containing a large intron in that part of the gene corresponding to the probe, or that there are two distinct renin genes. We have shown that the latter is the case by cloning and isolating two similar but distinct renin genes from DBA/2 mouse DNA. Restriction maps of the regions containing the two renin genes are presented, together with nucleotide sequence data locating a complete exon coding for amino acids 268-315 of mouse SMG renin.
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PMID:Molecular cloning of two distinct renin genes from the DBA/2 mouse. 632 70


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