Expression pattern of the deoxyribonuclease 1 gene: lessons from the Dnase1 knockout mouse.
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.
Napirei
Markus
M
Abteilung für Anatomie und Embryologie, Medizinische Fakultät, Ruhr-Universität Bochum, Universitätsstrasse 150, D-44780 Bochum, Germany. markus.napirei@ruhr-uni-bochum.de
Ricken
Albert
A
Eulitz
Dirk
D
Knoop
Heiko
H
Mannherz
Hans Georg
HG
D000818:Animals; D003433:Crosses, Genetic; D003850:Deoxyribonuclease I / Q000097:blood / Q000235:genetics* / Q000276:immunology; D020869:Gene Expression Profiling / Q000379:methods; D015971:Gene Expression Regulation, Enzymologic / Q000235:genetics*; D015151:Immunoblotting / Q000379:methods; D007178:Inbreeding; D007527:Isoenzymes / Q000235:genetics; D007962:Leukocytes / Q000201:enzymology; D008264:Macrophages / Q000201:enzymology; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D009928:Organ Specificity / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D014020:Tissue Extracts / Q000737:chemistry
D007527:Isoenzymes; D014020:Tissue Extracts; D003850:Deoxyribonuclease I