Disease relevance of ASL

• The delta 2-crystallin protein produced in Escherichia coli was purified to homogeneity and analyzed to determine the kinetic properties [1].

High impact information on ASL

• Published evidence indicates that the chick delta 1 crystallin gene encodes the major structural protein of embryonic lens fibres, whereas the closely related delta 2 gene may encode the urea-cycle enzyme argininosuccinate lyase (ASL) [2].
• For further analysis, the delta 2-crystallin cDNA was placed in the bacterial expression plasmid, pET-3d [1].
• It was shown to possess endogenous argininosuccinate lyase activity catalysing the reversible cleavage of argininosuccinate to give fumarate and arginine with an equilibrium constant of 1.8 +/- 0.23 mM [3].
• In one case, a truncated delta 2-crystallin promoter (-308/+24) in combination with the enhancer was also active in the Purkinje cells of the cerebellum of the transgenic mice, which could prove useful in future experiments [4].
• In the present investigation we have used transgenic mice to establish that both the chicken delta 1- and delta 2-crystallin enhancers are preferentially active in the mouse lens in combination with their homologous promoter and the chloramphenicol acetyltransferase (CAT) reporter gene [4].

Biological context of ASL

• Here we have quantified delta 1- and delta 2-crystallin mRNA in the lens, cornea, neural retina, heart, and brain at different stages of embryonic development and in 1-wk-old and 1-yr-old chickens by the polymerase chain reaction using internal delta 1 and delta 2 RNA standards [5].

Anatomical context of ASL

• A comparison of lens epithelium and fibers established that levels of delta 2-crystallin RNA are the same but those of delta 1-crystallin RNA are over 100-fold higher in fibers compared to epithelial cells [6].
• Finally, retinoic acid receptors (RAR beta) activated the delta 1-crystallin, but not the delta 2-crystallin enhancer in teh recombinant plasmids in cotransfected embryonic chicken lens epithelial cells treated with retinoic acid [4].

Associations of ASL with chemical compounds

• Lens-preferred activity of chicken delta 1- and delta 2-crystallin enhancers in transgenic mice and evidence for retinoic acid-responsive regulation of the delta 1-crystallin gene [4].
• Four histidine residues in the duck delta 2-crystallin [7].
• Argininosuccinate synthetase and argininosuccinate lyase catalyze the synthesis of arginine from citrulline in kidney and also serve as components of the urea cycle in liver of ureotelic animals [8].
• Argininosuccinate lyase mRNA was not induced by dibutyryl cAMP, dexamethasone, or a combination of the two agents [8].
• 4. Little arginine synthetase activity (argininosuccinate synthetase, E.C.6.3.4.5; and argininosuccinate lyase, E.C.4.3.2.1) was found in kidney, but none in the liver [9].

Other interactions of ASL

• This accumulation of delta-crystallin RNA during lens induction operates selectively on the delta 1-crystallin transcripts whereas delta 2-crystallin/argininsosuccinate lyase RNA is detectable at lower levels in all developing ocular tissues throughout this period [10].
• The duck delta 2-crystallin gene encodes an enzymatically-active argininosuccinate lyase while the delta 1-crystallin gene product, although 94% identical, is enzymatically inactive [7].

Analytical, diagnostic and therapeutic context of ASL

• Sequence analysis of pigeon delta-crystallin gene and its deduced primary structure. Comparison of avian delta-crystallins with and without endogenous argininosuccinate lyase activity [11].

References