Generalized glycogen storage and cardiomegaly in a knockout mouse model of Pompe disease
Generalized glycogen storage and cardiomegaly in a knockout mouse model of Pompe disease
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DOI：
10.1093/hmg/7.1.53
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发表时间：
1998-01-01
影响因子：
3.5
通讯作者：
van der Ploeg, AT
中科院分区：
文献类型：
--
作者：
Bijvoet, AGA;van de Kamp, EHM;van der Ploeg, AT
糖原累积病II型（GSDII;庞贝氏症）是由酸性α-葡糖苷酶的遗传性缺乏引起的影响心脏和骨骼肌的溶酶体病症。通过靶向破坏胚胎干细胞中的鼠酸性α-葡糖苷酶基因（Gaa）获得该疾病的小鼠模型。纯合子基因敲除小鼠（Gaa -/-）缺乏Gaa mRNA，并且具有几乎完全的酸性α-葡糖苷酶缺乏症，在出生后不久在肝脏、心脏和骨骼肌细胞中检测到含糖原的溶酶体，到13周龄时，已经形成大的糖原局灶性沉积物，肺泡间隙对酸性磷酸酶染色呈阳性，作为溶酶体病理学的标志，雄性和雌性基因敲除小鼠都是可育的，并且可以杂交产生后代。第一个出生的基因敲除小鼠目前9个月大，仍没有明显的临床症状，但心脏典型地增大，心电图异常，该模型的建立将有助于深入了解GSDII的发病机制，并为探讨不同治疗干预措施的有效性提供有价值的工具。
Glycogen storage disease type II (GSDII; Pompe disease), caused by inherited deficiency of acid alpha-glucosidase, is a lysosomal disorder affecting heart and skeletal muscles, A mouse model of this disease was obtained by targeted disruption of the murine acid alpha-glucosidase gene (Gaa) in embryonic stem cells. Homozygous knockout mice (Gaa -/-) lack Gaa mRNA and have a virtually complete acid alpha-glucosidase deficiency, Glycogen-containing lysosomes are detected soon after birth in liver, heart and skeletal muscle cells, By 13 weeks of age, large focal deposits of glycogen have formed, Vacuolar spaces stain positive for acid phosphatase as a sign of lysosomal pathology, Both male and female knockout mice are fertile and can be intercrossed to produce progeny The first born knockout mice are at present 9 months old, Overt clinical symptoms are still absent, but the heart is typically enlarged and the electrocardiogram is abnormal, The mouse model will help greatly to understand the pathogenic mechanism of GSDII and is a valuable instrument to explore the efficacy of different therapeutic interventions.