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PMID:15015938

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Citation

Napirei, M, Ricken, A, Eulitz, D, Knoop, H and Mannherz, HG (2004) Expression pattern of the deoxyribonuclease 1 gene: lessons from the Dnase1 knockout mouse. Biochem. J. 380:929-37

Abstract

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.

Links

PubMed PMC1224217 Online version:10.1042/BJ20040046

Keywords

Animals; Crosses, Genetic; Deoxyribonuclease I/blood; Deoxyribonuclease I/genetics; Deoxyribonuclease I/immunology; Gene Expression Profiling/methods; Gene Expression Regulation, Enzymologic/genetics; Immunoblotting/methods; Inbreeding; Isoenzymes/genetics; Leukocytes/enzymology; Macrophages/enzymology; Mice; Mice, Inbred C57BL; Mice, Inbred Strains; Mice, Knockout; Organ Specificity/genetics; Reverse Transcriptase Polymerase Chain Reaction/methods; Tissue Extracts/chemistry

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:DNAS1

GO:0004530: deoxyribonuclease I activity

ECO:0000315:

F

Figure 1 has homogenous Dnase1 (+) and homogenous mutant Dnase1 (-) mice. Dnase1 activity was able to be detected in (+) mice in several tissues including stomach, pituitary, kidney, lymph, and thyroid. Double mutants had no Dnase1 activity in any of the tissues.

complete
CACAO 9412

MOUSE:DNAS1

enables

GO:0004530: deoxyribonuclease I activity

ECO:0000315: mutant phenotype evidence used in manual assertion

F

Seeded From UniProt

complete

See also

References

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