Tissue-specific expression and subcellular localization of ALADIN, the absence of which causes human triple A syndrome.

[triple a syndrome]

Triple A syndrome is a rare genetic disorder caused by mutations in the achalasia -addisonianism-alacrima syndrome (AAAS ) gene which encodes a tryptophan aspartic acid (WD ) repeat-containing protein named alacrima -achalasia -adrenal insufficiency neurologic disorder (ALADIN ). Northern blot analysis shows that the 2 .1 kb AAAS mRNA is expressed in various tissues with stronger expression in testis and pancreas . We show that human ALADIN is a protein with an apparent molecular weight of 60 kDa , and expressed in the adrenal gland , pituitary gland and pancreas . Furthermore , biochemical analysis using anti-ALADIN antibody supports the previous finding of the localization of ALADIN in the nuclear membrane . The mutations S 544 G and S 544 X show that alteration of S 544 residue affects correct targeting of ALADIN to the nuclear membrane .