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KMID : 0918520120120010005
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Journal of the Korean Society of Inherited Metabolic Disease
2012 Volume.12 No. 1 p.5 ~ p.13
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Characterization of a Mucolipidoses Type Ⅱ Mouse Model and Therapeutic Implication of Lysosomal Enzyme Enriched Fraction Derived form Placenta
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Cho Sung-Yoon
Kim Ki-Yong
Kim Su-Jin
Sohn Young-Bae
Maeng Se-Hyun
Kim CHi-Hwa
Ko Ah-Ra
Song Jung-Han
Yeau Sung-Hee
Kim Kyung-Hyo
Jin Dong-Kyu
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Abstract
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I-cell disease (mucolipidosis type II; MIM 252500) and pseudo-Hurler polydystrophy (mucolipidosis type III; MIM 252600) are disorders caused by abnormal lysosomal transport in cells. The presence of numerous inclusion bodies in the cytoplasm of fibroblasts, a lack of mucopolysacchariduria, increased lysosomal enzyme activity in serum, and decreased GlcNAc-phosphotransferase activity are hallmark. Here, we attempted to investigate phenotypical and biochemical characteristics of the knockoutmouse of GlcNAc-phosphotransferase α/βsubunits; in addition, we also attempted to determine whether the lysosome enriched fraction derived from placenta can be beneficial to phenotype and biochemistry of the knockout mouse.We found that the knockout mouse failed to thrive and had low bone density, as is the case in human. In addition, skin fibroblasts from the animal had the same biochemical characteristics, including increased lysosomal enzyme activity in the culture media, in contrast to the relatively low enzyme activity within the cells. Intravenous injection of the lysosome rich fraction derived from placenta into the tail vein of the animal resulted in a gain of weight, while saline injected animals didn’t.In conclusion, our study demonstrated the phenotypical and iochemical similarities of the knockout mouse to a mucolipidosis type II patient and showed the therapeutic potential of the lysosome enriched fraction. We admit that a larger scale animal study will be needed; however, the disease model and the therapeutic potential of the lysosome enriched fraction will highlight the hope for a novel treatment approach to mucopolipidosis type II, for which no therapeutic modality is available.
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KEYWORD
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I-cell disease, mucolipidosis type Ⅱ, GNPTA, knockout mouse, GlcNAc-phosphotransferase
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