ALAS2过表达转基因小鼠呈现髓鞘损伤和肌萎缩

ALAS2 overexpressed transgenic mice exhibited demyelinating injury and muscle atrophy

氨基-γ-酮戊酸(δ-aminolevulinic acid,ALA)是血红素合成途径的第一个产物。ALA合酶(δ-aminolevulinic acid synthase,ALAS)有两种同工酶ALAS1和ALAS2,其中ALAS2仅在红系细胞表达。通过转基因技术实现全身过表达ALAS2的小鼠具有明显的肌萎缩表型,与同龄对照野生型小鼠相比,这种小鼠3月龄时神经反射实验反应时间延长,7月龄时疲劳转棒仪实验持续时间缩短,10月龄时脊髓和延髓在透射电镜下可见髓鞘板层松散且腓肠肌HE染色可见去神经支配样肌萎缩。ALA具有神经毒性,过量ALA对神经系统的损伤可能是该转基因小鼠肌萎缩成因之一。

δ-aminolevulinic acid(ALA)is the first product of the heme synthesis pathway.There are two kinds of ALA synthase(ALAS),ALAS1 and ALAS2,of which ALAS2 is expressed only in erythroid cells.Mice that achieved systemic overexpression of ALAS2 by transgenic technology had obvious amyotrophic phenotypes,when compared with wild-type mice of the same age,the response time of neural reflex experiment was prolonged,the duration of fatigue rotor experiment was shortened at 7 months of age,the spinal cord and medulla oblongata were loosed under transmission electron microscopy at 10 months of age,and denervation-like muscle atrophy was seen by gastrocnemius HE staining.The catalytic product of ALAS2 is neurotoxic,and the damage to the nervous system caused by excess ALA may be one of the causes of muscle atrophy in this transgenic mouse.