Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “RP2”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 19 recordsLinked to original sources
PubMed1989

Molecular genetics of androgen-inducible RP2 gene transcription in the mouse kidney.

Androgen control of the RP2 gene in the mouse kidney has been modified during evolution. In inbred mice (Mus domesticus), the concentrations of mRNAs encoded by RP2 undergo a 10- to 12-fold induction in response to testosterone; in other Mus species (e.g., Mus hortulanus and Mus caroli), induction ranges from none to about two- to fourfold. In this communication, we show that androgens induced RP2 transcription in M. domesticus, although this induction may not have fully accounted for the increase in mRNA levels. Reduced mRNA inducibility in M. hortulanus and in several other species was associated with an absence of transcriptional induction. Analysis of an interspecies backcross population indicated that the difference in RP2 inducibility between M. domesticus and M. hortulanus was due to a single Mendelian locus tightly linked (0 of 47 recombinants) to RP2. The RP2 gene was found to contain at least two promoters, only one of which was highly sensitive to testosterone. These results indicate that induction of the RP2 mRNAs, as well as interspecies variations in RP2 inducibility, are primarily a consequence of effects on this promoter.

Animals↗
PubMed1986

Amino acid sequence of the testosterone-regulated mouse kidney RP2 protein deduced from its complementary DNA sequence.

The major forms of testosterone-regulated RP2 messenger RNA (also known as MAK mRNA and pMK908) in the mouse kidney were characterized by examining cDNA and genomic clones. Three sizes of RP2 mRNA are detected by Northern blot analysis and these were shown to result from polyadenylation at three distinct sites within the primary transcript of this single-copy gene. The complete RP2 mRNA sequence was obtained from overlapping cDNA clones, revealing an open reading frame of 357 amino acids that corresponds to a protein of 40,365 daltons. The detection of RP2 mRNA in all tissues examined to date suggests that the RP2 protein may function in a housekeeping role in all cells. This is supported by the finding of a high percentage of G + C residues at the 5' end of the gene, including a sequence homologous to the binding site of the transcription factor Sp1, which has been suggested to affect the regulation of other housekeeping genes that have been characterized. An examination of the amino acid sequence indicates that the RP2 protein is proline-rich and is composed of alternating alpha-helix and beta-sheet regions. RP2 is probably not integrated into a membrane structure in the cell as it does not appear to contain hydrophobic regions capable of spanning a membrane.

Amino Acid Sequence↗
PubMed1991

Evolution of messenger RNA structure and regulation in the genus Mus: the androgen-inducible RP2 mRNAs.

The RP2 gene is one of several genes that are regulated by androgens in the mouse kidney. Previous studies have demonstrated that androgen inducibility of RP2 transcription varies among species within the genus Mus, indicating extensive evolutionary modification of the participating regulatory elements. Thus, while a five-fold induction of transcription occurs in M. domesticus, none is detectable in M. hortulanus or M. caroli. In the present paper, we have sequenced cDNAs representing the RP2 mRNAs of M. caroli and M. saxicola and have compared them with each other and with M. domesticus. Several findings from the sequence comparisons indicate that the encoded 41-kD polypeptide is physiologically functional. First, divergence within noncoding regions of the mRNAs exceeds that within coding regions. Second, the 357-codon open reading frame has been maintained among the species, with approximately 90% of the amino acid replacements being conservative. Finally, substitution rates at synonymous sites within the coding regions are from twofold to threefold greater than those at nonsynonymous sites. The genetic elements responsible for variations in RP2 inducibility among species were studied by cis/trans analyses of mice heterozygous for RP2 alleles, using a primer extension assay to measure expression of species-specific mRNAs. The results show that the absence of transcriptional induction in M. hortulanus is due to a cis-acting genetic element, while that in M. caroli is due to a trans-acting element. Thus, the androgen-resistant RP2 phenotypes of these two species derive from distinct genetic events.

Animals↗
PubMed1987

Evolution of steroid-inducible RP2 mRNA expression in the mouse kidney.

We have examined the structure and expression of mRNAs encoded by the androgen-inducible RP2 gene in the kidneys of nine mouse species within the genus Mus. There is considerable interspecies variation in the lengths of the major RP2 transcripts; some of this variation is due to the presence or absence of a B1 repetitive element in the 3'-untranslated region of the gene. In addition, the extent of RP2 mRNA induction by testosterone differs among the species. Two species show 10-20-fold induction, while others display a reduced response or none at all. Analysis of an interspecific hybrid indicates that the inducibility phenotype is inherited in an additive fashion. A correlation between RP2 inducibility and the time of formation of lineages within the Mus genus suggests that induction evolved in a stepwise fashion, with the acquisition of a modest hormonal response being followed by the appearance of a greater response. The interspecies variations in RP2 mRNA structure and regulation provide a useful model for the identification and study of genetic elements that elicit evolutionary alterations in steroid-modulated gene expression.

Animals↗
PubMed1979

Characterization and persistence of actinophage RP2 isolated from Streptomyces rimosus ATCC 10970.

While searching for true lysogens among oxytetracycline-producing Streptomyces rimosus strains, free phage particles were detected and isolated from a liquid culture of S. rimosus ATCC 10970 (R7). The actinophage, designated RP2, appears to be a typical temperate DNA phage producing turbid plaques on the sensitive strain S. rimosus R6. Electron microscopic examination of RP2 lysates showed that it belongs to group B of Bradley's morphological classification. The rate of RP2 adsoprption at 28 degrees C appeared to be low. The length of the latent period was about 6 h and the average burst size about 120 phage particles. The lysogenic nature of the host-virus system described was established on the basis of the following characteristics: spontaneous lysis frequency of 2 X 10(-6) per cell, resistance to curing with phage-specific antiserum, spontaneous curing frequency of less than 0.05% and immunity to superinfection with the homologous phage. Clear-plaque mutants of RP2, which failed to lysogenize sensitive cultures, arose at a frequency of 10(-5).

Adsorption↗
PubMed1991

Genetic localisation of the RP2 type of X linked retinitis pigmentosa in a large kindred.

Genetic linkage and deletion studies have led to the proposal that there are at least two loci on the X chromosome which are responsible for X linked retinitis pigmentosa (XLRP). One locus (RP3) has been closely defined by genetic linkage and deletion analyses and localised to the region between the ornithine transcarbamylase (OTC) and chronic granulomatous disease (CYBB) loci in Xp21.1-p11.4. The other locus (RP2) has been assigned by linkage analysis alone to region Xp11.4-p11.2, but its localisation is less well defined. The results of a multipoint linkage analysis of a single large XLRP kindred using eight informative loci provide further evidence on the localisation of RP2 to this region. The maximum likelihood location of this locus shows a multipoint lod score of 7.17 close to DXS255 (in Xp11.22) and TIMP (in Xp11.3-p11.23), neither of which show recombination with RP2, in an area extending from 2 cM proximal to DXS7 to 1 cM distal to DXS14 (approximate 95% confidence limits).

Bayes Theorem↗
PubMed1992

X-linked retinitis pigmentosa: functional phenotype of an RP2 genotype.

Rod- and cone-mediated function was studied with psychophysics and electroretinography in members of an X-linked retinitis pigmentosa pedigree with the RP2 genotype. An asymptomatic hemizygote with an early stage of the disease had cone dysfunction in the mid-periphery and an abnormal cone electroretinogram (ERG); rod function was normal. Hemizygotes with more advanced disease had cone and rod dysfunction in the mid-peripheral retina and cone dysfunction in the far periphery; cone and rod ERGs were abnormal. At very advanced stages, there was an absolute mid-peripheral scotoma and marked cone and rod dysfunction in the far peripheral and central retina. Cone and rod ERGs were severely abnormal or not detectable. Heterozygotes showed tapetal-like reflexes, patches of pigmentary retinopathy, and a range of functional findings from no detectable abnormalities to moderate levels of retinal dysfunction. There were regions of normal function adjacent to dysfunctional patches that had greater cone than rod sensitivity losses or comparable cone and rod losses. The results suggest that the phenotype of this RP2 genotype of X-linked retinitis pigmentosa, unlike other forms of retinitis pigmentosa, is first expressed as a cone photoreceptor system dysfunction, and as the disease progresses, both rod and cone systems are involved.

Adult↗
PubMed2026

InsightRP2-An Interdisciplinary Approach Toward Therapy Development in RP2-Associated Retinopathy.

Advancing the development of specific gene therapies for rare genetic eye disorders is a major challenge in modern translational vision research. It requires integrated clinical, molecular, mechanistic, and regulatory expertise, yet these aspects are often addressed in isolation. Combining complementary skills, knowledge, and expertise within an integrated, highly interactive research framework has the capacity to drive and advance therapeutic development. Moreover, early-stage involvement of patients and targeted clinical observation, alongside molecular and therapeutic research, potentially enable clinical trial readiness and support the translation of preclinical therapeutic innovations into clinical care. In this Perspective article, we present the InsightRP2 framework, an integrated translational strategy that incorporates clinical data, artificial intelligence-supported imaging analysis, experimental disease modeling, and adeno-associated virus design with the aim to facilitate the development of a targeted gene therapy for RP2-associated retinitis pigmentosa.

AAV↗
PubMed1990

Localization of the microsatellite probe DXS426 between DXS7 and DXS255 on Xp and linkage to X-linked retinitis pigmentosa.

The microsatellite marker DXS426 maps to the interval Xp21.1-Xp11.21, the chromosomal region which contains two loci for X-linked retinitis pigmentosa (XLRP; RP2 and RP3). We have refined the localization of DXS426 both physically, by mapping it to a deletion which spans the interval Xp21.3-Xp11.23, and genetically, by studying multiply informative crossovers which indicate that DXS426 lies between DXS7 and DXS255 (i.e., Xp11.4-Xp11.22). As this is the region which contains the RP2 gene, RP2 families could be identified on the basis of linkage of XLRP to DXS426. Multiply informative crossovers in two RP2 families indicate that the most likely location of the RP2 gene is between DXS426 and DXS7. DXS426 is therefore an important highly informative marker for the purposes of carrier detection and early diagnosis of RP2 and for the localization of the disease gene.

Base Sequence↗
PubMed1987

Magnetic resonance studies on the copper site of dopamine beta-monooxygenase in the presence of cyanide and azide anions.

In order to elucidate the coordination state of water molecules in the Cu(II) site of dopamine [( 3,4-dihydroxyphenyl)ethylamine] beta-monooxygenase, measurements of the paramagnetic 1H nuclear magnetic relaxation rate of solvent water in the enzyme solution containing cyanide or azide as an exogenous ligand were carried out to obtain the values of intrinsic paramagnetic relaxation rate decrements Rp1 and Rp2 for the ligand-enzyme 1:1 and 2:1 complexes, respectively. Rp1 (percent) values were 53 (pH 5.5) and 52 (pH 7.0) for cyanide and 38 (pH 5.5) and 32 (pH 7.0) for azide, while Rp2 (percent) values were 98 (pH 5.5) and 96 (pH 7.0) for azide. Although no Rp2 values for cyanide were obtained because of its reducing power at the Cu(II) site, the Rp1 and Rp2 values obtained above prove that the Cu(II) center has two coordinated water molecules that are exchangeable for exogenous ligands at either pH. Supporting evidence was provided by electron paramagnetic resonance (EPR) titration, in which the enzyme solution containing cyanide-enzyme (1:1) complex in an equal proportion to uncomplexed enzyme gave an observed paramagnetic relaxation rate decrement, Rp, of 23%. Another characteristic of the Rp1 and Rp2 values was their invariability with respect to pH, indicating that the three-dimensional structure of the Cu(II) site is pH-invariant within the range examined. Binding constants of ligand to enzyme Kb1 and Kb2 for 1:1 and 2:1 complex formation, respectively, were also determined through an analysis of the Rp values; it was found that Kb1 was larger than Kb2 irrespective of pH. (ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Medulla↗
PubMed1990

Development of an in vitro model of tumor progression using v-raf and v-raf/v-myc transformed rat liver epithelial cells: correlation of tumorigenicity with the downregulation of specific proteins.

A series of clonal cell lines were derived from rat liver epithelial cells after being infected with a defective retrovirus containing either v-raf (3611-MSV) or v-raf/v-myc(J2) together with a helper virus. These clones exhibited a different morphology from the regular cuboid shape of the control cells, infected only with the helper virus. All of the infected cell lines contained at least one full length copy of appropriate proviral DNA and expressed comparable levels of v-raf mRNA, although only the cells transformed with the v-raf/v-myc combination were capable of anchorage-independent growth in soft agar. All of the clones except the controls formed tumors in nude mice but with markedly different latency periods and growth rates. Thus, these cell lines represent an in vitro model for tumor progression. Two-dimensional polyacrylamide electrophoresis was used to investigate changes in cellular protein expression related to malignant conversion. The expression of three proteins of pI/Mr x 10(-3) 5.9-7.2/205 (RP1), 6.5-7.5/160 (RP2) and 4.0/85 (RP3) consistently matched the transformed phenotype. In particular the expression of RP1 and RP2 correlated with the relative tumorigenicity of the cell lines. Rat liver epithelial cell lines transformed by other protocols that did not involve v-raf also showed downregulation of these three polypeptides. Crude fractionation studies determined RP1 to be soluble and RP2 and RP3 to be membrane associated. RP2 was shown to be a glycoprotein containing mannose and galactose residues. These three proteins are consistent markers for the tumorigenic potential of rat liver epithelial cells.

Animals↗
PubMed1991

Influence of age at nutritional restriction on growth and sexual development of gilts.

Large White females were fed on a plane of nutrition close to ad libitum during the entire experimental period (CTRL group, n = 48) or restricted during a limited period of their growth (RP1 group: 28-62 kg, RP2 group: 64-96 kg, RP3 group: 97-131 kg, n = 48/group). Blood samples were taken before 200 and 230 days of age in order to detect cyclic gilts by assaying their progesterone levels. Animals were slaughtered at approximately 260 d of age and their genital tracts were examined. Overall feed intake, feed conversion ratio and daily gain were significantly lower in restricted than in CTRL gilts (average daily gain: 678, 680, 668 and 741 g/day respectively in RP1, RP2, RP3 and CTRL groups, P less than 0.05). At slaughter, animals from the 3 restricted groups has similar live weights but were lighter (152 vs 164 kg live weight, P less than 0.05) and leaner than CTRL (fat thickness: 29.5, 30.5, 28.0 and 34.1 mm respectively, in RP1, RP2, RP3 and CTRL groups). Respectively, 9, 43 and 76% of the gilts were puberal at 200, 230 and 260 days of age. The percentage of cyclic females was not influenced by treatment at 200 and 260 days of age while it was higher in CTRL (50%) and RP1 (56%) groups than in RP2 (35%) and RP3 (29%) groups at 230 days of age (P less than 0.05). At 260 days of age, ovarian and genital tract weights were not influenced by treatment either in prepuberal or in cyclic gilts.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed1986

Polymorphism in an androgen-regulated mouse gene is the result of the insertion of a B1 repetitive element into the transcription unit.

The single-copy RP2 gene in mice produces three major mRNAs, the abundances of which are significantly increased in the kidneys by the administration of testosterone. S1 nuclease analysis of the kidney mRNAs indicated that they differ in the lengths of their 3' untranslated regions as a result of the use of different polyadenylation sites. When the mRNAs from different inbred mouse strains were examined by Northern blot analysis, it was observed that the largest mRNA varies in size, whereas the sizes of the other mRNAs remain the same. In DBA/LiHa and DBA/2J mice, the largest mRNA is approximately 2,150 nucleotides long, whereas the corresponding mRNA in C57BL/6J and BALB/cJ mice is only 1,950 nucleotides in length. All of these strains also have RP2 mRNAs that are 1,450 and 1,350 nucleotides long. By S1 nuclease mapping and comparison of the sequence of cDNA clones representing these mRNAs in DBA/LiHa and C57BL/6J mice, we determined that this size difference or polymorphism observed in the largest mRNA is the result of the insertion of a member of the B1 family of repeats into the 3' untranslated region of the RP2 gene in DBA mice. This particular B1 repeat is transcribed by RNA polymerase III in vitro, and its transcriptional orientation is opposite to that of the RP2 transcript. The polymorphism described here is evidence for the mobility of B1 repetitive elements within the genome.

Animals↗
PubMed1988

Two different genes for X-linked retinitis pigmentosa.

Linkage analysis was carried out in three large multigenerational kindreds with X-linked retinitis pigmentosa using DNA markers on Xp. About 10% recombination has been found between the retinitis pigmentosa locus (RP2) and the marker locus DXS7, assigned to band Xp11.3, which was reported earlier to be closely linked to RP2 in several independent families. In the kindreds described in this paper, however, RP2 shows close linkage and no recombination with the marker loci OTC and DXS148, both assigned to Xp21, indicating that, contrary to previous linkage studies, there is evidence of an RP locus distal to DXS7. This suggests that X-linked retinitis pigmentosa is genetically heterogeneous, i.e., caused by mutations at different loci.

Female↗
PubMed1983

DNA sequence polymorphism in an androgen-regulated gene is associated with alteration in the encoded RNAs.

We have used plasmid pMK908, whose cDNA insert corresponds to an androgen-inducible RNA from mouse kidney, as a probe to study both the complementary genomic DNA and the encoded RNA sequences in several inbred strains of mice. A polymorphism in the 908 structural gene, revealed by Southern blotting of HindIII-generated DNA fragments, was found to map near the Gpi-1 and Tam-1 loci on chromosome 7. The 908 structural gene has been termed RP2. The 908 RNAs constitute a sequence-related group displaying extensive size heterogeneity. This heterogeneity, reflected in the size distribution of the RNA on electrophoretic blots, is controlled by a genetic site that is tightly linked to RP2. Thus, associated with polymorphism at RP2 is a change in the molecular size pattern of encoded transcripts.

Alleles↗
PubMed1991

Androgen modulation of DNA-binding factors in the mouse kidney.

Transcription of the RP2 gene in the mouse kidney is induced by androgens. This induction is species specific within the genus Mus. For example, the gene responds to androgens in Mus domesticus, but is refractory to hormone in the distantly related species M. caroli. In the present report we have characterized DNA-binding factors that recognize the 5' flanking region of the RP2 gene. One factor (termed RPBF-1) binds a DNA fragment spanning the region between -157 and -311 relative to the transcriptional start site. RPBF-1 is present in kidney nuclear extracts from both control and androgen-treated M. domesticus as well as from control M. caroli; however, in the latter species a distinct factor (termed RPBF-2) is induced by androgens and replaces RPBF-1. The androgen-dependent replacement of RPBF-1 by RPBF-2 is specific to the kidney of M. caroli. DNase-1 footprinting analyses indicate that the two factors recognize distinct, yet overlapping, regions of the RP2 promoter: RPBF-1 binds the region between -247 and -269, while RPBF-2 binds the region between -265 and -290. The RPBF-2-binding site contains a sequence that is homologous to that recognized by nuclear factor-1 (NF-1), suggesting that RPBF-2 is a NF-1-like factor. This is supported by competition experiments with synthetic oligonucleotides corresponding to the NF-1-binding site within the adenovirus origin of replication. Thus, androgens can modulate, in a species- and tissue-specific manner, DNA-binding factors that recognize promoter regions of genes.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Expression of the rat protamine 2 gene is suppressed at the level of transcription and translation.

We have compared the rat protamine 2 gene sequence (rP2) to that of the mouse protamine 2 (mP2) gene. The sequence encompasses 435 nucleotides of the coding region which includes an intron of 120 nucleotides, 461 nucleotides 5' to the coding sequence and 181 bases 3' to it. In the mouse the protamine 2 gene is abundantly transcribed and translated. The mP2 protein is initially synthesized as a precursor and then proteolytically processed to yield the mature protein. In contrast, in the rat, protamine 2 transcripts are present at 2-5% that found in the mouse and the mature protein has never been detected in spermatozoa. Although there is 92% nucleotide similarity between rat and mouse genes and 91% similarity of the predicted amino acid sequences, in vitro runoff transcription assays performed in either rat or mouse testis-derived transcription systems reveal that the rP2 promoter is only 30% as efficient a promoter as the mP2 promoter. Analyses of total sperm basic nuclear proteins extracted from epididymal sperm using a monoclonal antibody specific for protamine 2 suggest that the rat P2 mRNA is translated in vivo but is not properly processed. These results suggest that the lowered transcription rate and altered processing sites of the rat protamine 2 gene are likely to contribute to the lack of protamine 2 in rat spermatozoa.

Amino Acid Sequence↗
PubMed1987

Both P1 and P2 protamine genes are expressed in mouse, hamster, and rat.

To date, in mammals except for the mouse and human, only one protamine variant has been isolated from sperm. These mammalian protamines share amino acid sequence homology with mouse protamine 1 (mP1), the tyrosine-containing variant. Southern blot analysis of restriction enzyme digests of hamster and rat liver DNA reveals the presence of sequences homologous to mP1, and also to mouse protamine 2 (mP2) cDNAs. Northern blots of hamster and rat total testis RNA probed with mP2 cDNA confirm that the protamine 2 gene in these species is transcribed into two size classes of mRNA of approximately 830 and 700 nucleotides. However, the relative abundance of the rat and hamster protamine 2 mRNAs (rP2 and hP2) in total testis is approximately 50-fold lower and 2- to 5-fold lower, respectively, than the mouse protamine 2 mRNA. Northern blot analysis of hamster and rat testis polysome gradients demonstrates that although the amount of rP2 mRNA and hP2 mRNA is reduced, both are present on polysomes. The decreased expression of rat and hamster protamine 2 mRNA relative to their protamine 1 counterparts contrasts protamine expression in the mouse testis, where approximately equal amounts of mP1 and mP2 protamine mRNAs are present. These results suggest differential expression of the P1 and P2 protamine genes in three closely related mammals.

Animals↗