Induced mouse models of abnormal sphingolipid metabolism.

Only a limited number of genetic mouse models of abnormal sphingolipid metabolism are known to occur spontaneously. However, recent progress in the combined homologous recombination and embryonic stem cell technology allows inactivation of any genes of choice once they are cloned. Not only is it possible to generate mutant mouse lines that are equivalent to known human genetic disorders but genetic conditions unknown or highly unlikely to occur in humans, such as simultaneous inactivation of more than one gene, can also be created. Most of the human disorders due to genetic defects in sphingolipid catabolism have been duplicated in the mouse. With increasing activity in cloning of the enzymes involved in sphingolipid biosynthesis, genetic mouse models of abnormal sphingolipid biosynthesis are beginning to appear. These models have already provided invaluable insight into the metabolism and physiological functions of sphingolipids and are expected to be utilized extensively for evaluation of the pathogenesis and of treatment approaches of these genetic disorders.