Asl (argininosuccinate lyase) encodes a key enzyme in the urea cycle that catalyzes the breakdown of argininosuccinate to dicarboxylic acid fumarate and the amino acid arginine, a component of the citrulline-nitric oxide (Cit-NO)cycle. Humans with ASL deficiency develop Argininosuccinic aciduria (ASA), characterized by a persistent intellectual impairment, delayed motor skills and progressive hepatic disease.
This targeted mutation strain carries a FRT-flanked neomycin cassette in intron 9 that decreases expression and activity of the gene. These hypomorphic mice are reported to express 15-20% normal levels of protein. Homozygous mice die at 3-4 weeks of age. They show severe postnatal growth retardation, abnormal hair patterning, multiple organ system dysfunction, hyperammonemia, and nitric oxide deficiency. Liver transaminase levels are elevated in plasma, renal creatinine clearance is decreased, and systolic/diastolic blood pressures are elevated compared to wild-type mice. Histological defects are found in multiple organs, involving the immune, hematopoietic, and cardiovascular systems. Heterozygous animals have no phenotype. FLP excision of the neomycin cassette results in phenotypically normal mice.
LoxP sites in introns 6 and 9 make this a conditional allele for generating tissue-specific Cre-generated knockouts. Excision of exons 7-9 stops protein expression.
