Objective To breed and identify Mfge8 gene knock-out (Mfge8^{-/ -} ) C57BL/6 mice, and to examineserological and histological changes in these animals. Methods Genomic DNA was obtained from the tail of young miceand the genotype was determined by PCR and agarose gel electrophoresis. TUNEL assay was used to detect apoptotic cellsin the lung tissues of 12-week-old wild type (WT) and Mfge8^{-/ -} mice. Levels of anti-nuclear antibodies (ANA) and antiendothelialcell antibodies ( AECA) in the serum of 36-week-old WT and Mfge^{-/ -} mice were determined byimmunofluorescence. Results Knockout mice have been successfully generated and maintained that are homozygous forMfge8 gene deletion (Mfge8^{-/ -} ). The number of apoptotic cells in the lung tissues of 12-week-old Mfge8^{-/ -} mice was higherthan in WT mice. In addition, the serum of 36-weeks-old Mfge8^{-/ -} mice, but not WT mice, was positive for ANA andAECA. Conclusions Mfge8 knockout mice with the C57BL/6 genetic background demonstrate a greater susceptibility to autoimmune disease.