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

Systemic lupus erythematosus (SLE) is an autoimmune disease that has high morbidity and can result in multi-organ damage. SLE is characterized by dysregulated activation of T- and B-lymphocytes and the production of autoantibodies directed against nuclear components. The endonuclease deoxyribonuclease 1 (DNase1) is abundant in blood and a subset of SLE patients have mutations in DNASE1. Furthermore, a report showed that Dnase1-deficient mice develop an SLE-like disease, but these mice also carry a deletion of the gene adjacent to Dnase1, which encodes the chaperone TRAP1/HSP75. We generated a murine strain deficient in Dnase1 with an intact Trap1 gene to examine if a lack of DNase1 is responsible for the development of a spontaneous SLE-like disease. We show that the Dnase1-deficient mice do indeed develop an SLE-like phenotype with elevated autoantibody production by 9 months and kidney damage by 12 months. Notably, this model recapitulates the female bias seen in human SLE patients since female Dnase1-deficient mice produced the highest concentrations of autoantibodies and had more severe kidney damage than males. Since there is currently no cure for SLE the protective role of DNase1 as demonstrated in our study remains of great therapeutic interest.
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PMID:Dnase1-deficient mice spontaneously develop a systemic lupus erythematosus-like disease. 3075 51