| First Author | Shiao T | Year | 1999 |
| Journal | Pharmacogenetics | Volume | 9 |
| Issue | 2 | Pages | 145-53 |
| PubMed ID | 10376761 | Mgi Jnum | J:56601 |
| Mgi Id | MGI:1341968 | Citation | Shiao T, et al. (1999) Four amino acid changes are associated with the Aldh3a1 locus polymorphism in mice which may be responsible for corneal sensitivity to ultraviolet light. Pharmacogenetics 9(2):145-53 |
| abstractText | We studied the phenotype and the nucleotide sequence for the cDNAs of the AInh3a1(a) and Aldh3a1(c) allelic forms of the dioxin-inducible cytosolic aldehyde dehydrogenase (ALDN3A1) present in inbred mouse strains. This gene is constitutively expressed in cornea, stomach, skin, urinary bladder and lungs. The Aldh3a1(a) allele is found in most inbred mouse strains and codes for a 'high-activity' corneal enzyme compared to the 'low-activity' encoded by the Aldh3a1(c) allele in SWR/J strain, The 'low-activity' variant is associated with extensive corneal clouding after a single exposure to ultraviolet light, The ALDH3A1 phenotype was examined in tissues from inbred mouse strains carrying the Aldh3a1(a) allele including, SJL/J, C57BL/6 J/Ibg, DBA/2 J/Ibg, C3H/Ibg and the Aldh3a1(c) allele (SWR/J). Only trace levels of ALDH3A1 activity were found in all SWR/J tissues. All other strains had significant levels of ALDH3A1 activity in eye, stomach, shin, less in urinary bladder and lungs and only trace amounts in liver. However, no differences were found in corneal and stomach ALDH3A1 mRNA levels between the 'low-' and 'high-activity' variants. A 1556-bp ALDH3AI cDNA fragment, containing the entire coding region plus 5' and 3' untranslated regions, was amplified by reverse transcriptase-polymerase chain reaction from SWR/J and DBA/ 2 J/Ibg mouse strains, Sequence analysis revealed 13 nucleotide changes in the Aldh3a1(c) allele. Four of these changes result in G88R, I154N, H305R and I352V substitutions, whereas nine changes are silent. The I154N disrupts a potential a helix, which belongs to the Rossmann fold. Replacement of Arg with the more ionizable I-Iis at position 305 of a beta strand might directly affect catalytic activity of the enzyme. It is likely that structural changes associated with these amino acid changes are responsible for the loss of ALDH3AI enzymatic activity in SWR/J mice. Pharmacogenetics 9:145-153 (C) 1999 Lippincott Williams & Wilkins. |
