Mouse renin gene structure, evolution and function

Burt, David W.; Beecroft, Linda J.; Mullins, John J.; Pioli, David; George, Helen; Brooks, Jeanie I.; Walker, John; Brammar, William J.

doi:10.1515/9783111649788-035

Cited by 14 publications

(6 citation statements)

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“…pRn34 is a 6.5-kilobase (kb) BamHI fragment from the Renid gene containing the 5' flanking region, exon 1, and part of the first intron, inserted into the BamHI site of pUC8. This BamHI A fragment was originally isolated from a A DBA renin genomic clone, DBARn12, containing the Renid gene (9). pBa6 contains a 5-kb BamHI fragment from the 5' flanking region ofthe Ren22d gene inserted into the BamHI site of pUC8.…”

Section: Methodsmentioning

confidence: 99%

Negative control elements and cAMP responsive sequences in the tissue-specific expression of mouse renin genes.

Nakamura

Burt

Paul

et al. 1989

Proc. Natl. Acad. Sci. U.S.A.

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The 5' flanking regions of the mouse renin genes (Renid and Ren2d) contain putative negative control and cAMP responsive elements. Sequence analysis shows additionally that these putative control elements in the Ren2d gene are interrupted by a 160-base-pair insertion. To document the functions of these elements, we isolated these regions and fused them to the reporter gene chloramphenicol acetyltransferase (CAT), which was linked upstream to a thymidine kinase (TK) promoter (pUTKAT1). The chimeric constructs were transfected into mouse pituitary tumor AtT-20 and human choriocarcinoma JEG-3 cells. At the basal unstimulated condition, Renid 5' flanking sequence in the sense orientation inhibited basal CAT expression from the TK promoter of pUTKAT1, whereas the same sequence in the antisense orientation did not. The 5' flanking region of Ren2d had no inhibitory effect on basal CAT expression. These data demonstrate that the negative control element is functional in Ren1d but is nonfunctional in Ren2d, suggesting that the 160-base-pair insertion in Ren2d interferes with the function of the negative control elements. In response to 8-bromo-cAMP, both renin genes increased transcription 3-fold, suggesting a functional cis action of the cAMP responsive element in both genes. These data may be important in the understanding of the regulation of the tissue-specific expression of mouse renin genes.

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Section: Methodsmentioning

confidence: 99%

Negative control elements and cAMP responsive sequences in the tissue-specific expression of mouse renin genes.

Nakamura

Burt

Paul

et al. 1989

Proc. Natl. Acad. Sci. U.S.A.

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“…With the cloning of the renin gene [11] and the development ofhighly specific and sensitive hybridization procedures [12], it has become possible to determine the extent of renin-gene expression outside the kidney. Using these techniques we now have evidence for widespread extra-renal renin-gene expression in the rat, with major differences between organs, providing the basis for an important ubiquitous local regulatory system the role of which may extend beyond the circulation.…”

Section: Introductionmentioning

confidence: 99%

Expression of the renin gene in extra-renal tissues of the rat

Samani

Swales

Brammar³

1988

Biochemical Journal

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Expression of the renin gene in several rat organs is demonstrated by the detection of renin mRNA using a ribonuclease-protection technique. In two of these sites, the brain and the liver, renin mRNA levels are unaffected by changes in dietary salt which markedly affect renal renin mRNA levels. The findings provide the basis for an important ubiquitous local regulatory role for the renin-angiotensin system extending beyond the circulation.

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“…DNA sequence features unique to Ren-2 include the presence of a proviral intracisternal A particle located downstream and a B2 repetitive element situated upstream of Ren-2 (10, 11). However, Ren-JD and Ren-2 display a high degree of homology across the structural region of the gene having the same genomic organization (9,12,13) and sharing >96% sequence identity at the level of the transcript (9). At the genomic level (including intronic sequences) Ren-JD and Ren-2 share -95% sequence identity (ref.…”

mentioning

confidence: 99%

Targeted integration of the Ren-1D locus in mouse embryonic stem cells.

Miller¹,

McPheat²,

Potts³

1992

Proc. Natl. Acad. Sci. U.S.A.

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We have introduced a Ren-ID targeting vector Into embryonic stem cells containing the two highly homologous mouse renin genes Ren-ID and Ren-2. Using a polymerase chain reaction (PCR) screen designed to detect targeted integration at Ren-ID and Ren-2, we isolated 15 targeted embryonic stem cell clones, all of which had undergone a gene conversion event at the Ren-iD locus. We did not isolate any clones in which the incoming DNA had recombined with Ren-2. Over the region encompassed by our transgene, Ren-ID and Ren-2 display >95% homology. Our results suggest that the machinery driving gene targeting by means of homologous recombination in mammalian cells is capable of dis hing between these two sequences. Construction of transgenic mice with the embryonic stem cells reported here carrying a mutated renin gene will permit a greater understanding of the functions of the Ren-iD and Ren-2 gene products and their relative contribution to cardiovascular homeostasis.Renin is an aspartyl protease that catalyzes the initial and rate-limiting step in the conversion of angiotensinogen to the potent vasoactive hormone angiotensin II. The primary site of synthesis ofcirculating renin is thejuxtaglomerular cells of the kidney. However, a number of other extrarenal sites of renin biosynthesis have now been described, including the adrenal gland, liver, and testes (1-3). The function of this extrarenal renin is not known.In mice, high levels of renin and renin mRNA can also be found in the submandibular gland (4, 5). Mice are polymorphic for the number of renin genes, certain inbred strains harboring one gene (Ren-JC) and others containing two genes (Ren-JD and Ren-2). The mouse renin genes are located on chromosome 1 (6), with the Ren-2 gene situated -20 kilobases (kb) upstream ofRen-JD (relative to the transcriptional direction) in two-gene animals; both genes are transcribed in the same direction (7). The presence of the Ren-2 gene appears to be the result of a duplication of the renin locus t3-10 million years ago (8, 9). DNA sequence features unique to Ren-2 include the presence of a proviral intracisternal A particle located downstream and a B2 repetitive element situated upstream of Ren-2 (10, 11). However, Ren-JD and Ren-2 display a high degree of homology across the structural region of the gene having the same genomic organization (9,12,13) and sharing >96% sequence identity at the level of the transcript (9). At the genomic level (including intronic sequences) Ren-JD and Ren-2 share -95% sequence identity (ref. 13; unpublished results). The three mouse renin genes display similar but distinct tissue specificities (1,3,14,15) (Fig. 1) gg of linearized pTk-Ren-neo at 500 OLF and 250 V in a 0.4-cm pathlength electroporation chamber (Bio-Rad). These cells were then plated out on ten 9-cm Petri dishes. Selection with G418 (250 Ag/ml) and gancyclovir (2 puM) was applied after Abbreviation: ES, embryonic stem. tTo whom reprint requests should be sent at present address:

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Mouse renin gene structure, evolution and function

Cited by 14 publications

References 0 publications

Negative control elements and cAMP responsive sequences in the tissue-specific expression of mouse renin genes.

Negative control elements and cAMP responsive sequences in the tissue-specific expression of mouse renin genes.

Expression of the renin gene in extra-renal tissues of the rat

Targeted integration of the Ren-1D locus in mouse embryonic stem cells.

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