Gene knock-out mouse models have become gold standards for delineating molecular and functional roles of specific genes. In an attempt to generate such models for neurological disorders, we have initiated studies to disrupt apolipoprotein D (ApoD) gene in mouse embryonic stem cells. We have used rat ApoD cDNA probe to screen the 129/svj mouse genomic library. Eight genomic clones of ApoD have been isolated and partially characterized. These isogeneic clones will be used to make targeting vectors for gene disruption.