Faust J R, Rodman J S, Daniel P F, Dice J F, Bronson R T
Department of Physiology, Tufts University School of Medicine, Boston, Massachusetts 02111.
J Biol Chem. 1994 Apr 1;269(13):10150-5.
In this study, we show that two biochemical markers of neuronal ceroid lipofuscinoses (NCLs) are present in a mutant mouse (mnd/mnd) that exhibits symptoms of the disease. Subunit c of the mitochondrial F1F0-ATP synthase, a proteolipid that accumulates in storage bodies of most forms of NCL and several animal models, is dramatically increased in mnd/mnd mouse brain, kidney, liver, heart, and pancreas. Interestingly, another related proteolipid, subunit c of the vacuolar H(+)-ATPase, also accumulates in several mnd/mnd tissues. The molar ratio of the vacuolar subunit c to the F1F0 subunit c is approximately one to two in enriched storage bodies from brain. The relative accumulation of the vacuolar subunit c correlates with its abundance in normal tissues. It appears in decreasing amounts in brain, kidney, and liver and is not detected in heart or pancreas. Aged mice and two mutant mouse lines, juvenile bare (jb) and mucopolysaccharidosis, type VII (gusmps), did not accumulate either of these proteolipids. Dolichol-linked oligosaccharides also accumulate in NCLs and are increased 17-fold in mnd/mnd mouse brain. Thus, mnd/mnd mice seem to be an excellent model for NCLs since they not only share clinical signs and histopathology, but also two biochemical markers. The accumulation of the vacuolar subunit c in this model may prove to be a marker for distinguishing different forms of NCLs.
在本研究中，我们发现神经元蜡样脂褐质沉积症（NCLs）的两种生化标志物存在于表现出该疾病症状的突变小鼠（mnd/mnd）中。线粒体F1F0 - ATP合酶的c亚基，一种在大多数形式的NCL和几种动物模型的储存体中积累的蛋白脂质，在mnd/mnd小鼠的脑、肾、肝、心和胰腺中显著增加。有趣的是，另一种相关的蛋白脂质，即液泡H(+) - ATP酶的c亚基，也在mnd/mnd小鼠的多个组织中积累。在从脑中富集的储存体中，液泡c亚基与F1F0 c亚基的摩尔比约为1:2。液泡c亚基的相对积累与其在正常组织中的丰度相关。它在脑、肾和肝中的含量逐渐减少，在心脏或胰腺中未检测到。老年小鼠以及两种突变小鼠品系，幼年裸鼠（jb）和黏多糖贮积症VII型（gusmps），均未积累这两种蛋白脂质中的任何一种。多萜醇连接的寡糖也在NCLs中积累，并且在mnd/mnd小鼠脑中增加了17倍。因此，mnd/mnd小鼠似乎是NCLs的一个优秀模型，因为它们不仅具有共同的临床症状和组织病理学特征，还具有两种生化标志物。在这个模型中液泡c亚基的积累可能被证明是区分不同形式NCLs的一个标志物。
