In this strain, the allele replaces the entire coding region of the microRNA-223 (Mir223) gene with a frt-flanked neomycin (neo) resistance cassette, abolishing gene function. They also harbor the CD45.1 (Ly5.1 or Ptprca) allele rather than the CD45.2 (Ly5.2 or Ptprcb) allele normally present in C57BL/6 mice. Homozygous miR-223- mice are viable, fertile, and normal in size. After endotoxin challenge, these mice exhibit an increase in aspartate aminotransferase (ALT), blood urea nitrogen (BUN) and creatine kinase (CK) levels due to widespread tissue destruction, including hepatocyte necrosis and intralobular haemorrhage. MiR-223 plays a key role in controlling steatosis-to-non-alcoholic steatohepatitis (NASH) progression by inhibiting hepatic Cxcl10 and Taz expression in high-fat diet fed mice. They also develop inflammatory lung pathology characterized by areas of atelectasis, increased cellularity within the parenchyma, and inflammatory infiltration into the interstitium. Granulocytes from miR-223- mice are hypermature, hypersensitive to activating stimuli, and display increased fungicidal activity. These mice have an expanded granulocytic compartment resulting from a cellautonomous increase in the number of granulocyte progenitors. These mice may be useful for studying granulocyte production and inflammatory response.
