|Lysyl oxidases: Cloning and characterization of the fourth and the fifth human lysyl oxidase isoenzymes, and the consequences of a targeted inactivation of the first described lysyl oxidase isoenzyme in mice|
Lysyl oxidases play an important role in the formation of lysine-derived cross-links in collagens and elastin. These cross-links in turn stabilize the structures of these proteins in the extracellular matrix. Moreover, lysyl oxidases may have additional unknown intracellular or even intranuclear functions. The critical role of lysyl oxidase activity is well demonstrated by the defects in the collagen and elastin fibers that are seen in the Menkes and OHS diseases, their animal models, and also in lathyrism.
To date, little is known about the tissue, developmental stage, or substrate specifities of the emerging lysyl oxidase isoenzymes. Identification and characterization of these new isoenzymes and homozygous inactivation of one of them can be expected to give valuable information about their functions in a living organism. Therefore, the goals of this study were:
To attempt to identify, clone, and characterize additional human lysyl oxidase isoenzymes. Subsequent goals were to study expression of the mRNAs for these isoenzymes in human tissues and to produce a recombinant protein in a mammalian expression system to study whether this protein is located in the extracellular space or whether it is found intracellularly or even intranuclearly.
To produce mice lacking the activity of the first characterized lysyl oxidase isoenzyme (Lox) using homologous recombination in embryonic stem cells, and to analyse the consequence of the lack of this activity in the homozygous Lox-/- mice.