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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recombination is believed to prevent genetic deterioration in sexual populations because it allows conservation of functional genotypes by removing deleterious mutations. Moreover, evidence that non-recombining segments of a genome deteriorate is provided by genetic experiments in Drosophila and yeast. Y chromosomes generally do not recombine along most of their length, and thus Y chromosome genes, despite having been selectively maintained for their function, could be lost from the genome. Here we present definitive evidence that functional Y genes can be lost from the mammalian genome. TSPY genes must have been selectively maintained on the mammalian Y chromosome since before the radiation of eutheria, 80 million years ago, as they are found conserved on the Y chromosome in two mammalian orders: primate and artiodactyl. We have now identified TSPY on the rodent Y chromosome, in mouse and rat. The gene structure and expression of rat TSPY suggest that it is a functional, testis-specific gene, but the closely related mouse gene, Tspy, has clearly become non-functional, producing only low levels of aberrantly spliced transcripts. Thus TSPY lost its function in the mouse lineage after its divergence from the rat lineage. So, in the case of Tspy at least, the absence of recombination does appear to have led to the loss of a functional gene.
Hum Mol Genet 1998 Mar
PMID:Rodent Y chromosome TSPY gene is functional in rat and non-functional in mouse. 946 17

Dosage compensation for X-linked genes in mammals is accomplished by inactivating one of the two X chromosomes in females, a process involving a regulatory gene, Xist (X-inactive specific transcript). Xist maps to the X-inactivation centre and is expressed from the inactive X chromosome in female somatic cells and at the time of X inactivation during spermatogenesis in the male. In female preimplantation embryos, Xist demonstrates imprinting in that the paternal allele inherited from the sperm is preferentially expressed. This preferential paternal Xist expression is correlated with paternal X inactivation in the extraembryonic lineages at the blastocyst stage. We have analysed a 233-bp Xist promoter fragment (nt -220 to +13) for its ability to direct appropriate expression and its regulation by DNA methylation. This minimal promoter sequence directs expression of the luciferase reporter gene following injection of the construct into one-cell embryos. In vitro methylation of the construct before injection represses transcription. In six different transgenic lines, expression of the Xist promoter-luciferase transgene occurs only in the testis of the males (as for the endogenous Xist gene). The testis-specific expression is correlated with hypomethylation of the transgene, although to different extents in different lines. Following paternal transmission, expression of the Xist promoter-luciferase construct in preimplantation embryos is correlated with degree of hypomethylation in the testis and the degree of hypomethylation of the transgene in embryos at the morula stage. It is concluded that the patterns of methylation of the transgene in sperm (and in microinjected transgenes) can regulate the activity of the Xist promoter in the preimplantation embryo and thus support the hypothesis that gametic methylation patterns govern imprinted expression of the endogenous Xist gene in development.
Mol Reprod Dev 1998 Apr
PMID:Expression of an Xist promoter-luciferase construct during spermatogenesis and in preimplantation embryos: regulation by DNA methylation. 950 86

Cell-specific isoforms of the alpha1 subunit of the L-type voltage-dependent calcium channel (VDCC) have unique pharmacological reactivities. Prior sequence analysis of nucleotide bases 3908-6077 of the VDCC alpha1 subunit expressed in rat testis differed from cardiac sequences only in a 84 base pair region corresponding to exons 31/32 encoding a putative dihydropyridine binding region. We now report that sequence analysis of bases 3048-3936 identifies a second difference between the rat testis and rat cardiac alpha1 sequence in a 60 base pair region corresponding to exons 21/22 and encoding another putative dihydropyridine binding site. Variable VDCC exons 21/22 and 31/32 and their linking introns were sequenced using genomic DNA from rat lung as template, providing evidence that the rat testis and cardiac alpha1 isoforms are products of the same gene. Reverse transcription in-situ polymerase chain reaction (PCR) with frozen sections of rat testis was carried out with primers identifying the testis-specific exon 32 of the VDCC alpha1 subunit. PCR products were confined to seminiferous tubules and were associated with the germ cell lineage from Type A spermatogonia to mature spermatozoa. Close coupling of testis alpha1 VDCC gene transcription and translation was established by in-situ immunolabelling of serial frozen sections with a monoclonal antibody (IIF7) directed against epitopes on rabbit skeletal muscle L-type VDCC alpha1. Western blot analysis of rat proteins extracted from heart, skeletal muscle, testis and spermatozoa which were reactive with the IIF7 antibody detected primarily 175-220 kDa proteins in the size range of VDCC. These data unequivocally demonstrate that an L-type VDCC is expressed in rat testis and that VDCC isoforms from rat testis and heart differ in deduced amino acid composition in and around potential binding sites for calcium channel blocking drugs such as the dihydropyridines.
Mol Hum Reprod 1998 Mar
PMID:Alternative splicing of exons in the alpha1 subunit of the rat testis L-type voltage-dependent calcium channel generates germ line-specific dihydropyridine binding sites. 957 Feb 67

Limited information is available concerning the regulation of growth hormone-releasing hormone (GHRH) gene expression in the hypothalamus, largely because of the lack of a suitable cellular model. In an attempt to immortalize hypothalamic GHRH-producing neurons, we have generated a transgenic mouse model which expresses the simian virus 40 (SV40) T-antigen gene (Tag) under the control of the GHRH gene promoter. The transgene contains approximately 5 kb of mouse GHRH gene sequences, including 3.5 kb of the 5'-flanking region, the entire hypothalamic exon 1 and 1.5 kb of intron 1, fused to the SV40 Tag gene. This construct was microinjected into fertilized oocytes. Fourteen of 96 mice born had integrated the transgene. These mice were fertile and showed no signs of central or peripheral tumors. The pattern of expression of the SV40 Tag gene was analyzed in four different transgenic lines by RT-PCR. The tissues tested include: hypothalamus, pituitary, cortex, cerebellum, spinal cord, adrenal, testis, spleen and lung. Transgene expression was consistently detected in the hypothalamus of all lines. In addition, SV40 Tag expression was also detected in the hypothalamus by Northern blot analysis in two of the transgenic lines. SV40 Tag expression was also detected in the testis of all transgenic lines by RT-PCR. This result was not expected since the GHRH gene sequences present in the transgene do not include the testis-specific transcription initiation site previously described. This suggests that GHRH gene expression in the mouse testis can be directed by regulatory sequences located downstream of the testis specific transcription start site. We conclude that the promoter region of the GHRH gene included in this construct contains the regulatory elements necessary to drive hypothalamic and testis expression in vivo. In addition, all mice from one of the transgenic lines developed cataracts in both eyes. SV40 Tag expression was detected not only in eyes with cataracts, but also, to a lesser extent, in eyes from other transgenic lines. Furthermore, the endogenous GHRH gene was found to be expressed in the eyes of normal mice.
Mol Cell Endocrinol 1998 Feb
PMID:Expression of a fusion gene consisting of the mouse growth hormone-releasing hormone gene promoter linked to the SV40 T-antigen gene in transgenic mice. 960 18

Expression of the testis-specific histone TH2B, the phosphoprotein p19, and the transition proteins TP1 and TP2, was localized in the rat testis and quantified, using in situ hybridization of their mRNAs with radiolabeled probes and image analysis. In a first study, expression was assessed during testicular development between day 2 and day 65 postpartum. TH2B mRNAs appeared first in preleptotene spermatocytes (PL) on day 12 and in pachytene spermatocytes (PS) on day 18; p19 mRNAs were present in PS from day 18 onward, and TP1 and TP2 mRNAs were detected in round spermatids (RS) from day 32 onward. In the second trial, the expression of these four genes was studied throughout the cycle of spermatogenic epithelium in mature animals. TH2B mRNAs were localized in B spermatogonia at stage V, and in PL at stages VII and VIII but no longer in leptotene and zygotene spermatocytes. Thereafter, TH2B mRNAs were observed in PS from stages III-IV to XIII. The steady-state mRNA level per cell was high in PS with a maximum at stages IX-X. p19 mRNAs were present in PS from stages III-IV onward and in RS up to stages 1-2 of spermiogenesis. The maximum mRNA level per cell was observed in PS between stages VII and XIII. The presence of TP1 mRNAs was restricted to spermatids from steps 6 to 15-16 of spermiogenesis while TP2 mRNAs were detected in spermatids only between step 7 and step 13. The highest steady-state amounts of mRNAs were observed between step 7 and step 14 for TP1 and between step 10 and step 12 for TP2.
Mol Reprod Dev 1998 Sep
PMID:Localization and quantitative expression of mRNAs encoding the testis-specific histone TH2B, the phosphoprotein p19, the transition proteins 1 and 2 during pubertal development and throughout the spermatogenic cycle of the rat. 971 14

The sperm surface fertilin complex was first described in the guinea pig where it was found as a heterodimer of alpha and beta subunits, both of which were proposed to play a role in sperm-oolemma recognition and plasma membrane fusion during fertilisation. Whilst the beta subunit is apparently testis-specific, the finding of low levels of fertilin alpha in nonreproductive tissues has cast some doubt on a unique role in fertilisation. Moreover, the absence of a functional fertilin alpha gene in the human would imply that this gene product is not absolutely essential for fertilisation, although it could play a facilitatory role. We now describe the organisation and sequence of the fertilin alpha genes in a range of primates, including the great apes, and find that the gorilla gene, like that of the human, is non-functional.
Mol Reprod Dev 1998 Sep
PMID:Sequence analysis of a variety of primate fertilin alpha genes: evidence for non-functional genes in the gorilla and man. 971 22

The gene encoding the testis-specific isoform of mouse poly(A) binding protein (Pabp2) has been isolated and sequenced. Unexpectedly, comparison of the sequence of genomic and cDNAs demonstrated that the Pabp2 gene lacks introns, whereas all other functional Pabp genes in plants, amphibians, and mammals contain introns. Thus, the mouse Pabp2 gene is a retroposon, created by synthesizing a reverse transcriptase copy of a processed mRNA and inserting the copy into the genome. The Pabp2 retroposon is unusual because it is functional: previous work demonstrates that its promoter drives the accumulation of Pabp2 mRNA in meiotic and early haploid spermatogenic cells, and the Pabp2 mRNA encodes a protein whose size and RNA-binding specificities are characteristic of PABP in plants, yeast, and mammals (Kleene et al. 1994). Two novel factors can be implicated in the retention of function of the Pabp2 retroposon. First, the promoter of the Pabp2 gene is not derived from its intron-containing progenitor, Pabp1. Second, mRNAs encoding somatic PABP isoform, PABP1, are present at high levels in meiotic and haploid spermatogenic cells. Both features contrast with the phosphoglycerate kinase 2 retroposon, which is believed to compensate for the depletion of the somatic isoform due to X-chromosome inactivation in meiotic spermatogenic cells. We also document that more functional retroposons are expressed in meiotic and haploid spermatogenic cells than in any other tissue and speculate that transcriptional derepression in spermatogenic cells favors the creation of expressed retroposons.
J Mol Evol 1998 Sep
PMID:The mouse gene encoding the testis-specific isoform of Poly(A) binding protein (Pabp2) is an expressed retroposon: intimations that gene expression in spermatogenic cells facilitates the creation of new genes. 973 54

Previous data indicated a tissue-specific regulation of mitochondrial pyruvate dehydrogenase (PDH) complex, especially in the brain and testis. The lack of biochemical data on the rat testis PDH limits comparative analysis between testis and liver enzymes. Therefore, we have isolated a cDNA clone encoding rat testis PDH E1 alpha isoform, determined its nucleotide sequence, studied the tissue-specific expression, and characterized the recombinant protein produced in bacteria, compared to the liver counterpart. Our cDNA clone (2.2 kb) contained the identical open reading frame (from nt 974 to 2149) with that previously reported (Cullingford et al., 1993 Biochim Biophys Acta 1216:149-153) but contained a long 5' untranslated region, which has little identity to the other clone. Northern blot confirmed testis-specific expression of this isoform. Genomic DNA analyses by PCR amplification suggested this clone is a gene product distinct from its X-linked somatic counterpart. Our biochemical and kinetic analyses revealed that the purified recombinant rat testis PDH E1 (containing both E1 alpha and E1 beta subunits) was enzymatically active and phosphorylated in vitro by purified PDH-kinase p48 or p45, similar to the recombinant human liver enzyme. Our current data thus indicate that the differential regulation of testis PDH observed in the animal model may result from differential modulation of PDH-kinase or -phosphatase in this tissue rather than the presence of functionally different PDH E1 subunit.
Comp Biochem Physiol B Biochem Mol Biol 1998 May
PMID:Pyruvate dehydrogenase E1 alpha isoform in rat testis: cDNA cloning, characterization, and biochemical comparison of the recombinant testis and liver enzymes. 978 90

The most important event determining the nuclear status of sperm cells is the replacement of histones by protamines, which are the basic nuclear proteins of mature spermatozoa. A first step in this exchange is the displacement of histones by transition proteins (TP). Our study demonstrates, for the first time, the sequential expression of the testis-specific histone (H1t) and the transition proteins (TP1 and TP2) during normal human spermatogenesis. H1t mRNA could only be detected in the cytoplasm of mid and late pachytene spermatocytes. Concomitant with the onset of H1t transcription, the H1t protein appeared in the nuclei of pachytene spermatocytes and remain as a nuclear protein constituent up to step 5 spermatids. While transition protein 1 gene TNP-1 mRNA was present in spermatids from step 2 to early step 4, the TP1 protein occured, with temporal delay, in the nuclei of step 3 and step 4 spermatids. The TP2 protein was observed in the nuclei of spermatids from step 1 to step 5. The transition protein 2 gene TNP-2 mRNA was only detected by reverse transcription-polymerase chain reaction, but not on paraffin sections. These data demonstrate a strong temporal association between H1t gene transcription and synthesis of the H1t protein. Since the TP1 protein appeared with temporal delay we can assume that the corresponding TNP-1 mRNA is translationally delayed.
Mol Hum Reprod 1998 Oct
PMID:Expression of mRNA and protein of nucleoproteins during human spermiogenesis. 980 74

Hypothesizing that genes important in meiotic processes in mammals might have evolutionarily conserved counterparts in lower organisms, we used the yeast IME2 meiotic gene (serine threonine kinase) as a probe for screening a mouse testis cDNA library. This screening resulted in identification of a novel putative serine threonine kinase. Although it did not exhibit significant homology to IME2, it did show significant sequence homology to the Tousled kinase in Arabidopsis. Tousled is associated with various differentiative processes including differentiation of the reproductive organs. The new murine gene was designated accordingly Tlk (Tousled like kinase). Tousled like kinase sequences have been reported to occur in C. elegans and in the human. Positive hybridization signals obtained in zooblot analysis suggest evolutionary conservation of Tlk throughout the phylogenetic ladder. Four distinct Tlk transcripts were detected in mouse testis, at least one of which is testis-specific. Northern and in situ hybridization analyses revealed that in normal testis, Tlk is expressed predominantly in pachytene spermatocytes and in round spermatids. Transcripts differ from one another in their 3' untranslated region, resulting from use of different polyadenylation sites, and in the length of their 5' region. Within the coding region, three of the putative peptides share the kinase and C-terminal domains but differ in their N-terminal domain, suggesting that the latter may be involved in the regulation of Tlk's function. We conclude that although Tlk might have an essential role in all tissues, these kinases are likely to take part in the complex array of phosphorylations involved in regulating spermatogenesis.
Mol Reprod Dev 1999 Apr
PMID:Tlk, a novel evolutionarily conserved murine serine threonine kinase, encodes multiple testis transcripts. 1009 19


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