Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.30.2 (endonuclease)
 18,621 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The tissue distribution of deoxyribonuclease 1 (DNASE1, DNase I), a Ca2+ and Mg2+/Mn2+-dependent secretory endonuclease, has previously been investigated. However, most of these studies did not account for the existence of different members of the DNASE1 gene family, did not differentiate between endogenous DNASE1 protein synthesis and its extracellular occurrence or were not performed with methods allowing both a sensitive and a specific detection. Now we re-examined the DNASE1 gene expression pattern by taking advantage of the Dnase1 knockout mouse model. Direct comparison of samples derived from wild-type (Dnase1+/+) and knockout (Dnase1-/-) mice allowed an unambiguous detection of Dnase1 gene expression at the mRNA and protein level. For the detection of Dnase1 activity, we developed a highly sensitive nuclease zymogram method. We observed high Dnase1 gene expression in the parotid and submandibular gland as well as in the kidney and duodenum, intermediate expression in the ileum, mesenterial lymph nodes, liver, ventral prostate, epididymis, ovary and stomach, and low expression in the sublingual, preputial, coagulation and pituitary gland. We report for the first time the lachrymal and thyroid glands, the urinary bladder and the eye to be Dnase1-expressing organs as well. Since Dnase1 knockout mice with the 129xC57Bl/6 mixed genetic background have indicated the protection against an anti-DNA autoimmune response as a new physiological function of Dnase1, knowledge of the physiological sites of its synthesis might prove helpful to find new therapeutic strategies.
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PMID:Expression pattern of the deoxyribonuclease 1 gene: lessons from the Dnase1 knockout mouse. 1501 38

Dicer1, an RNase III endonuclease, is indispensable for the maturation of miRNA and siRNA, which control gene expression through the RNAi pathway. The diverse functions of miRNA involving multiple developmental processes have been elucidated, but the role of Dicer1 in spermatogenesis is just beginning to be revealed. Mice lacking Dicer1 were reported to be embryonic lethal at E7.5. In the present study, mice with a Dicer1 conditional allele were crossed with Vasa-cre transgenic mice to delete Dicer1 as early as the prospermatogonia stage (at E15). At P40, seminiferous tubules of Dicer1 deficient mice showed several aberrant phenotypes. A large number of apoptotic germ cells were detected by the terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling (TUNEL) assay, but several events in meiosis of spermatocytes appeared unaffected. The mutant mice were found to be sterile, likely due to the extensive decrease in number and morphological abnormalities of mature sperm in the epididymis, which, together with the numerous haploid cells in the testis, indicated a severely affected transition from round to functional elongated spermatozoa. Additionally, we found milder phenotypes when Dicer1 was inactivated in later stages of spermatogenesis in Stra8-cre and Pgk2-cre transgenic mice. In conclusion, our findings suggest that the loss of Dicer1 has a continuous and cumulative effect on the process of spermatogenesis and blocks the germ cells in the stage of round spermatids to a large extent, ultimately leading to the generation of abnormal sperm.
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PMID:Inactivation of Dicer1 has a severe cumulative impact on the formation of mature germ cells in mouse testes. 2256 35

Ribonucleic acid (RNA) was previously thought to remain inside cells as an intermediate between genes and proteins during translation. However, it is now estimated that 98% of the mammalian genomic output is transcribed as noncoding RNAs, which are involved in diverse gene expression regulatory mechanisms and can be transferred from one cell to another through extracellular communication. For instance, microRNAs are 22-nucleotide-long noncoding RNAs that are generated by endonuclease cleavage of precursors inside the cells and are secreted as extracellular microRNAs to regulate target cell posttranscriptional gene expression via RNA interference. We and others have shown that different populations of microRNAs are expressed in distinct regions of the human epididymis and regulate the expression of target genes that are involved in the control of male fertility as indicated by knock-out mouse models. Importantly, some microRNAs, including the microRNA-888 (miR-888) cluster that is exclusively expressed in the reproductive system of human and nonhuman primates, are released in the sperm-surrounding fluid in the epididymis via extracellular vesicles, the so-called epididymosomes. In addition to interacting with the membrane of maturing spermatozoa, these extracellular vesicles containing microRNAs communicate with epithelial cells located downstream from their release site, suggesting a role in the luminal exocrine control of epididymal functions. Apart from their potential roles as mediators of intercellular communication within the epididymis, these extracellular microRNAs are potent molecular targets for the noninvasive diagnosis of male infertility.
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PMID:Extracellular microRNAs from the epididymis as potential mediators of cell-to-cell communication. 2617 95