Two related proteolipids and dolichol-linked oligosaccharides accumulate in motor neuron degeneration mice (mnd/mnd), a model for neuronal ceroid lipofuscinosis.
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.
Faust
J R
JR
Department of Physiology, Tufts University School of Medicine, Boston, Massachusetts 02111.
Rodman
J S
JS
Daniel
P F
PF
Dice
J F
JF
Bronson
R T
RT
D000595:Amino Acid Sequence; D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D002240:Carbohydrate Sequence; D002417:Cattle; D002851:Chromatography, High Pressure Liquid; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D046911:Macromolecular Substances; D051379:Mice; D008818:Mice, Neurologic Mutants; D008969:Molecular Sequence Data; D009046:Motor Neurons / Q000378:metabolism* / Q000473:pathology; D016538:Mucopolysaccharidosis VII / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism; D009472:Neuronal Ceroid-Lipofuscinoses / Q000378:metabolism*; D009928:Organ Specificity; D015388:Organelles / Q000378:metabolism; D010179:Pancreas / Q000378:metabolism; D011104:Polyisoprenyl Phosphate Oligosaccharides / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism; D011510:Proteolipids / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*; D006180:Proton-Translocating ATPases / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D012756:Sheep / Q000378:metabolism; D014617:Vacuoles / Q000201:enzymology
D046911:Macromolecular Substances; D011104:Polyisoprenyl Phosphate Oligosaccharides; D011510:Proteolipids; D006180:Proton-Translocating ATPases