Partial characterization of a human zinc-deficiency syndrome by differential display

The effect of the acrodermatitis enteropathica mutation (AE) on gene expres sion was investigated using differential display. Two differentially expres sed cDNAs were partially characterized. The NA8 cDNA (HT(11)A anchor and HA P 8 random primer pair) was expressed in greater quantity in normal fibrobl asts, was 249 bp, and hybridized to three mRNA species (2 kb, 1 kb, 0.8 kb) . Northern blot analysis indicated that the relative amounts of the AE mRNA species were reduced by 73%, 75%, and 52%, respectively. The cDNA sequence exhibited 92-93% homology to the human cytochrome oxidase subunit II, as a nalyzed through the GenBank database. The AEG4 cDNA species (HT(11)G anchor and HAP 4 random, primer pair) was expressed in greater quantity in AE fib roblasts, was 197 bp, and hybridized to two mRNA species (9 kb, 4 kb). Nort hern blot analysis indicated that the 9-kb mRNA species was present equally in AE and normal cells, but the 4-kb mRNA species was only present in the AE fibroblasts. The cDNA sequence exhibited 92% homology to LINE1 human ret rotransposons, as analyzed through the GenBank database. The functional rel ationship between the mutation and the reduced expression of cytochrome oxi dase subunit II is unknown at this time and needs to be addressed. The incr eased expression of the LINE1 element in AE fibroblasts may be indicative o f an insertion mutation affecting the mRNA of a protein involved in zinc tr ansport, a prospect which requires further investigation.