Expression profile and down-regulation of argininosuccinate synthetase in hepatocellular carcinoma in a transgenic mouse model.

Background: Argininosuccinate synthetase (ASS) participates in urea and nitric oxide production and is a rate-limiting enzyme in arginine biosynthesis. Regulation of ASS expression appears complex and dynamic. In addition to transcriptional regulation, a novel post-transcriptional regulation affecting nuclear precursor RNA stability has been reported.

A transgenic approach to study argininosuccinate synthetase gene expression.

Background: Argininosuccinate synthetase (ASS) participates in urea, nitric oxide and arginine production. Besides transcriptional regulation, a post-transcriptional regulation affecting nuclear precursor RNA stability has been reported. To study whether such post-transcriptional regulation underlines particular temporal and spatial ASS expression, and to investigate how human ASS gene behaves in a mouse background, a transgenic mouse system using a modified bacterial artificial chromosome carrying the human ASS gene tagged with EGFP was employed.

The mutation spectrum of the phenylalanine hydroxylase (PAH) gene and associated haplotypes reveal ethnic heterogeneity in the Taiwanese population.

Phenylalanine hydroxylase (PAH) deficiency is responsible for most cases of phenylketonuria (PKU). In this study of the PAH mutation spectrum in the Taiwanese population, 139 alleles were identified including 34 different mutations. The V190G, Q267R and F392I mutations are first reported in this study.

Modulation of formation of the 3'-end of the human argininosuccinate synthetase mRNA by GT-repeat polymorphism.

Microsatellites are abundant in the human genome and may acquire context-dependent functions. A highly polymorphic GT microsatellite is located downstream of the poly(A) signal of the human argininosuccinate synthetase (ASS1) gene. The ASS1 participates in urea and nitric oxide production and is a rate-limiting enzyme in arginine biosynthesis.

Simultaneous assessment of the effects of exonic mutations on RNA splicing and protein functions.

To simultaneously assess the effects of exonic mutations on RNA splicing and protein functions, we report here an intron-inclusive cDNA (Intinc) expression system. As a test model, twenty-four mutations in exon 9 of the phenylalanine hydroxylase (PAH) gene were examined in an Intinc expression plasmid composed of the PAH cDNA with the exon 9 flanked by its authentic introns. When the PAH enzyme activities from the Intinc plasmid-transfected cells were compared to those of a standard cDNA expression system, five mutations resulted in significant relative differences in PAH activities attributed to altered exon 9-inclusive mRNA levels.