120 research outputs found
Sulfatide activator protein : alternative splicing that generates three mRNAs and a newly found mutation responsible for a clinical disease
The sulfatide activator protein, also known as SAP-1, is derived from a gene that generates an mRNA coding for four homologous proteins. Its physiological function is to stimulate hydrolysis of sulfatide by arylsulfatase A in vivo. A genetic defect in the sulfatide activator results in a metabolic disorder similar to classical metachromatic leukodystrophy, which is itself caused by a genetic defect in arylsulfatase A. In a patient with sulfatide activator deficiency, a nucleotide transversion G722----C (counted from A of the initiation codon ATG) was found in the mRNA of the sulfatide activator precursor, resulting in the substitution of serine for Cys241 in the mature sulfatide activator. The remainder of the coding sequence was completely normal except for a polymorphism C to T in position 1389, which does not change the amino acid sequence. The patient produces at least three different forms of mRNA for the precursor. Two of them include a stretch of an additional 9 and 6 bases, respectively, within the sulfatide activator coding region. In normal individuals this stretch of additional bases has also been observed. This could be explained by the presence of a small 9-base pair exon which can be introduced, or not, by alternative splicing as a stretch of 9 or 6 bases into the mature mRNA. The shortest form of the mRNA yields an active sulfatide activator (FĆ¼rst, W., Schubert, J., Machleidt, W., Meier, H. E., and Sandhoff, K. (1990) Eur. J. Biochem. 192, 709-714)
Neurological deficits and glycosphingolipid accumulation in saposin B deficient mice
Saposin B derives from the multi-functional precursor, prosaposin, and functions as an activity enhancer for several glycosphingolipid (GSL) hydrolases. Mutations in saposin B present in humans with phenotypes resembling metachromatic leukodystrophy. To gain insight into saposin B's physiological functions, a specific deficiency was created in mice by a knock-in mutation of an essential cysteine in exon 7 of the prosaposin locus. No saposin B protein was detected in the homozygotes (Bā/ā) mice, whereas prosaposin, and saposins A, C and D were at normal levels. Bā/ā mice exhibited slowly progressive neuromotor deterioration and minor head tremor by 15 months. Excess hydroxy and non-hydroxy fatty acid sulfatide levels were present in brain and kidney. Alcian blue positive (sulfatide) storage cells were found in the brain, spinal cord and kidney. Ultrastructural analyses showed lamellar inclusion material in the kidney, sciatic nerve, brain and spinal cord tissues. Lactosylceramide (LacCer) and globotriaosylceramide (TriCer) were increased in various tissues of Bā/ā mice supporting the in vivo role of saposin B in the degradation of these lipids. CD68 positive microglial cells and activated GFAP positive astrocytes showed a proinflammatory response in the brains of Bā/ā mice. These findings delineate the roles of saposin B for the in vivo degradation of several GSLs and its primary function in maintenance of CNS function. Bā/ā provide a useful model for understanding the contributions of this saposin to GSL metabolism and homeostasis
Die Gleichstellung nach dem Heimarbeitsgesetz
Bibliothek Weltwirtschaft Kiel A153,038 / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekSIGLEDEGerman
Zur Emission radioaktiver Stoffe aus Kernkraftwerken mit Leichtwasserreaktoren im Normalbetrieb
Zur Emission radioaktiver Stoffe aus Kernkraftwerken mit Leichtwasserreaktoren im Normalbetrieb
Lehrgang fĆ¼r Deutsch zur DurchfĆ¼hrung der Schulreform in Krefeld vom 22. November bis 4. Dezember 1926
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