A mouse gene knockout model for juvenile ceroid-lipofuscinosis (Batten disease)

The human hereditary ceroid-lipofuscinoses are a group of autosomal recessi vely inherited diseases characterized by massive accumulations of autofluor escent lysosomal storage bodies in the cells of many tissues and by neurona l degeneration throughout the central nervous system, There are a number of clinically and genetically distinct forms of ceroid-lipofuscinosis, the mo st common of which is the juvenile type, also known as Batten disease and C LN3, To study the mechanisms that lead to pathology in CLN3 and to evaluate potential therapies, a mouse model has been generated by targeted disrupti on of the mouse ortholog of the CLN3 gene (Cln3), As in affected humans, mi ce homozygous for the disrupted Cln3 allele show accumulation of autofluore scent storage material in neurons and other cell types. The storage materia l consists of membrane-bounded intracellular inclusions with ultrastructura l features typical of the ceroid-lipofuscinoses. The accumulation of this s torage material validates the Cln3 knockout mice as a model for the human d isorder. (C) 1999 Wiley-Liss,Inc.