The protein encoded by the Lum (lumican) gene, lumican, is a member of the small leucine-rich proteoglycan family, the predominant corneal keratan sulfate proteoglycan, is also found in interstitial extracellular matrices. Lumican regulates collagen fibril structure and is involved with the innate immune response, wound healing and neutrophil migration. These mice carry a targeted mutation for the Lum gene in which exon 2 is replaced by a NEO cassette. Mice that are homozygous for the targeted mutation are viable and fertile, but homozygous female mice on the C57BL/6 background are not good breeders. Homozygotes on the C57BL/6J background have loose skin around the neck, and older mice develop spontaneous lesion and tears of the skin. No gene product (protein) is detected by Western blot analysis of eye tissue, bone marrow extracts and peritoneal lavage from homozygotes. Homozygotes exhibit hyperextensible (8-fold reduced tensile strength) skin with abnormal collagen fibril structure and develop corneal opacity. Histological analysis of homozygotes reveals disorganized disorganized collagen fibrils with increased diameter in connective tissues of the skin, tendon, and cornea. Polymorphonuclear neutrophils from homozygotes exhibit poor chemotactic migration. In cell culture assays peritoneal macrophages (from homozygotes) exhibit defective phagocytosis of gram-negative bacteria. In response to LPS challenge, peritoneal macrophages and polymorphonuclear neutrophils (from homozygotes) exhibit a sub-normal production of proinflammatory cytokine (TNFalpha and IL6) production. Mutant mice are hyporesponsive to LPS-induced septic shock compared to wildtype controls and clearance of Gram-negative bacterial infections is impaired. During backcrossing, the Y chromosome may not have been fixed to the C57BL/6J genetic background.

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In this strain a PGK-neo cassette replaces sequence including exon 2 of the Lum (lumican) gene. These mice exhibit corneal opacity, poor wound healing, are hyporesponsive to LPS-induced sepsis and may be useful in studies of corneal dystrophy, extracellular matrix and neutrophil migration during the immune response.

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