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.
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.
Hansis
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IHF Institute for Hormone and Fertility Research, University of Hamburg, Germany.
Jähner
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Spiess
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Boettcher
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Ivell
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D015094:3-Hydroxyacyl CoA Dehydrogenases; D000544:Alzheimer Disease / Q000235:genetics*; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D018076:DNA, Complementary; D005786:Gene Expression Regulation; D006801:Humans; D007985:Leydig Cells / Q000378:metabolism*; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009845:Oligospermia / Q000378:metabolism*; D013737:Testis / Q000166:cytology / Q000378:metabolism*
D002352:Carrier Proteins; D018076:DNA, Complementary; D015094:3-Hydroxyacyl CoA Dehydrogenases; C108634:HSD17B10 protein, human; C458480:Hsd17b10 protein, mouse