The gene for the Alzheimer-associated beta-amyloid-binding protein (ERAB) is differentially expressed in the testicular Leydig cells of the azoospermic by w/w(v) mouse.

TY - JOUR

T1 - The gene for the Alzheimer-associated beta-amyloid-binding protein (ERAB) is differentially expressed in the testicular Leydig cells of the azoospermic by w/w(v) mouse.

AU - Hansis, C

AU - Jähner, D

AU - Spiess, Andrej-Nikolai

AU - Boettcher, K

AU - Ivell, R

PY - 1998

Y1 - 1998

N2 - In order to discover possible new testicular paracrine factors involved in the establishment of spermatogenesis, a modified differential display reverse transcription, polymerase chain reaction (DDRT-PCR) procedure was used to detect gene transcripts preferentially expressed in the testes of the azoospermic w/w(v) mutant mouse. One of the differentially expressed gene products showed partial similarity to members of the short-chain alcohol dehydrogenase family of enzymes. This cDNA fragment was used to obtain the full-length mouse cDNA sequence, which initially showed moderate similarity to a 20beta-steroid dehydrogenase from lower organisms, and later shown to have >85% similarity to a novel endoplasmic-reticulum-associated-binding protein (ERAB) from the human brain, implicated in Alzheimer's disease. A recently cloned bovine sequence also of high similarity suggests that this molecule might also represent an isozyme of 3-hydroxyacyl-CoA dehydrogenase. Using the mouse cDNA as probe, northern hybridization showed enrichment of the transcript to the testicular Leydig cells, and showed a specific approximately 20-fold enrichment in the azoospermic mouse testis. The level of the testicular ERAB transcript does not seem to change through puberty, suggesting that a lack of germ cells alone is not responsible for the up-regulation in the w/w(v) testis. Using the three-dimensional coordinates of the published 20beta-hydroxysteroid dehydrogenase structure as template, it was additionally possible to construct a molecular model of the novel protein which showed it to have a very similar structure to this enzyme, including the substrate-binding domain.

AB - In order to discover possible new testicular paracrine factors involved in the establishment of spermatogenesis, a modified differential display reverse transcription, polymerase chain reaction (DDRT-PCR) procedure was used to detect gene transcripts preferentially expressed in the testes of the azoospermic w/w(v) mutant mouse. One of the differentially expressed gene products showed partial similarity to members of the short-chain alcohol dehydrogenase family of enzymes. This cDNA fragment was used to obtain the full-length mouse cDNA sequence, which initially showed moderate similarity to a 20beta-steroid dehydrogenase from lower organisms, and later shown to have >85% similarity to a novel endoplasmic-reticulum-associated-binding protein (ERAB) from the human brain, implicated in Alzheimer's disease. A recently cloned bovine sequence also of high similarity suggests that this molecule might also represent an isozyme of 3-hydroxyacyl-CoA dehydrogenase. Using the mouse cDNA as probe, northern hybridization showed enrichment of the transcript to the testicular Leydig cells, and showed a specific approximately 20-fold enrichment in the azoospermic mouse testis. The level of the testicular ERAB transcript does not seem to change through puberty, suggesting that a lack of germ cells alone is not responsible for the up-regulation in the w/w(v) testis. Using the three-dimensional coordinates of the published 20beta-hydroxysteroid dehydrogenase structure as template, it was additionally possible to construct a molecular model of the novel protein which showed it to have a very similar structure to this enzyme, including the substrate-binding domain.

M3 - SCORING: Zeitschriftenaufsatz

VL - 258

SP - 53

EP - 60

IS - 1

M1 - 1

ER -