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M-CSF transgenic mice: Role of M-CSF in infection and autoimmunity

: Bernier, T.; Halter, R.; Paul, D.; Rittinghausen, S.; Emmendörffer, A.


Experimental and Toxicologic Pathology 53 (2001), No.2-3, pp.165-173
ISSN: 0940-2993
Journal Article
Fraunhofer ITA ( ITEM) ()
lupus; macrophage colony; stimulating factor; cytokines; autoimmunity; macrophage; listeria

In this study, transgenic CD2F1 mouse lines (C-1.1-C-1.11) bearing a transgene encoding the murine growth factor M-CSF under the control of the liver specific alpha-1-antitrypsin gene promoter were generated. Transgenic C-1.4 mice showed elevated expression of transgene-encoded M-CSF in the liver and displayed a 2-3-fold increase of M-CSF plasma levels and of macrophage numbers in the liver as compared with non-transgenic littermates. M-CSF transgenic mice showed increased resistance against sublethal i.v. infections with Listeria monocytogenes as compared with infected non-transgenic mice. To investigate the influence of M-CSF in murine systemic lupus erythematosus (SLE), the M-CSF transgenic mouse line C-1.4 was bred into the genetic background of SLE-prone MRL+/+ mice. The resulting C-1.4/MRL transgenic mice bearing increased endogenous M-CSF levels showed consistently lower levels of anti-ss-DNA autoantibodies as compared with non-transgenic MRL+/+ mice. The life span of the C- 1.4/MRL transgenic mice and the severity of the disease in these mice remained unchanged as compared with their non-transgenic littermates. It is concluded that in addition to M-CSF further factors must be involved in the acceleration of the autoimmune disease in SLE prone MRL/lpr mice.