Ian Hornstra, M.D., Ph.D.

DEPARTMENT OF Internal Medicine
Keywords: extracellular matrix, knockout mice, lysyl oxidase

The research focus of my laboratory is lysyl oxidases. Lysyl oxidases are copper-containing monoamine oxidase enzymes that catalyze the conversion of lysine residues in collagen and elastin to allysine. Allysine residues in collagen and elastin spontaneously condense to form highly stable crosslinks that impart great mechanical strength in collagen and elastin.

Currently, five different lysyl oxidases are known to exist in both humans and mice. These five forms of lysyl oxidases reside on five different chromosomes. To study the role of lysyl oxidases in growth and development and maintenance of the extracellular matrix, the lysyl oxidase genes are being cloned and characterized, and individual gene knockout vectors are being constructed. Mice genetically deficient in lysyl oxidase-1 and -2 have been constructed and are being analyzed. Lysyl oxidase-1 deficiency appears lethal at parturition in mice, whereas lysyl oxidase-2 deficiency causes no severe developmental phenotype.

In addition to the knockout models, the various lysyl oxidases are being expressed in vitro to attempt to elucidate substrate specificities. The various tissue specificities and expression patterns of the lysyl oxidases are being investigated by analysis of individual promoter sequences in transfection assays and by in vivo footprinting.