THE GENE FOR THE ALZHEIMER-ASSOCIATED BETA-AMYLOID-BINDING PROTEIN (ERAB) IS DIFFERENTIALLY EXPRESSED IN THE TESTICULAR LEYDIG-CELLS OF THEAZOOSPERMIC BY W W(V) MOUSE/

In order to discover possible new testicular paracrine factors involve d in the establishment of spermatogenesis, a modified differential dis play reverse transcription, polymerase chain reaction (DDRT-PCR) proce dure was used to detect gene transcripts preferentially expressed in t he testes of the azoospermic w/w(v) mutant mouse. One of the different ially expressed gene products showed partial similarity to members of the short-chain alcohol dehydrogenase family of enzymes. This cDNA fra gment was used to obtain the full-length mouse cDNA sequence, which in itially showed moderate similarity to a 20 beta-steroid dehydrogenase from lower organisms, and later shown to have > 85 % similarity to a n ovel endoplasmic-reticulum-associated-binding protein (ERAB) from the human brain, implicated in Alzheimer's disease. A recently cloned bovi ne sequence also of high similarity suggests that this molecule might also represent an isozyme of 3-hydroxyacyl-CoA dehydrogenase. Using th e mouse cDNA as probe, northern hybridization showed enrichment of the transcript to the testicular Leydig cells, and showed a specific appr oximately 20-fold enrichment in the azoospermic mouse testis. The leve l of the testicular ERAB transcript does not seem to change through pu berty, suggesting that a lack of germ cells alone is not responsible f or the up-regulation in the w/w(v) testis. Using the three-dimensional coordinates of the published 20 beta-hydroxysteroid dehydrogenase str ucture as template, it was additionally possible to construct a molecu lar model of the novel protein which showed it to have a very similar structure to this enzyme, including the substrate-binding domain.