Katz M L, Shibuya H, Liu P C, Kaur S, Gao C L, Johnson G S
Department of Ophthalmology, University of Missouri, Columbia 65212, USA.
J Neurosci Res. 1999 Aug 15;57(4):551-6.
The human hereditary ceroid-lipofuscinoses are a group of autosomal recessively inherited diseases characterized by massive accumulations of autofluorescent lysosomal storage bodies in the cells of many tissues and by neuronal degeneration throughout the central nervous system. There are a number of clinically and genetically distinct forms of ceroid-lipofuscinosis, the most common of which is the juvenile type, also known as Batten disease and CLN3. To study the mechanisms that lead to pathology in CLN3 and to evaluate potential therapies, a mouse model has been generated by targeted disruption of the mouse ortholog of the CLN3 gene (Cln3). As in affected humans, mice homozygous for the disrupted Cln3 allele show accumulation of autofluorescent storage material in neurons and other cell types. The storage material consists of membrane-bounded intracellular inclusions with ultrastructural features typical of the ceroid-lipofuscinoses. The accumulation of this storage material validates the Cln3 knockout mice as a model for the human disorder.
人类遗传性脑黄斑变性是一组常染色体隐性遗传疾病，其特征是在许多组织的细胞中大量积累自发荧光的溶酶体储存体，并在整个中枢神经系统中出现神经元退化。脑黄斑变性有多种临床和遗传上不同的形式，其中最常见的是青少年型，也称为巴顿病和CLN3。为了研究导致CLN3病理的机制并评估潜在的治疗方法，通过靶向破坏CLN3基因（Cln3）的小鼠直系同源基因，建立了一个小鼠模型。与受影响的人类一样，Cln3等位基因被破坏的纯合小鼠在神经元和其他细胞类型中显示出自发荧光储存物质的积累。储存物质由具有脑黄斑变性典型超微结构特征的膜结合细胞内包涵体组成。这种储存物质的积累证实了Cln3基因敲除小鼠可作为人类疾病的模型。
