Abstract:
:This review deals with the pharmacological properties of an alkylated monosaccharide mimetic, N-butyldeoxynojirimycin (NB-DNJ). This compound is of pharmacogenetic interest because one of its biological effects in mice - impairment of spermatogenesis, leading to male infertility - depends greatly on the genetic background of the animal. In susceptible mice, administration of NB-DNJ perturbs the formation of an organelle, the acrosome, in early post-meiotic male germ cells. In all recipient mice, irrespective of reproductive phenotype, NB-DNJ has a similar biochemical effect: inhibition of the glucosylceramidase beta-glucosidase 2 and subsequent elevation of glucosylceramide, a glycosphingolipid. The questions that we now need to address are: how can glucosylceramide specifically affect early acrosome formation, and why is this contingent on genetic factors? Here we discuss relevant aspects of reproductive biology, the metabolism and cell biology of sphingolipids, and complex trait analysis; we also present a speculative model that takes our observations into account.
journal_name
Pharmacogenomicsjournal_title
Pharmacogenomicsauthors
van der Spoel AC,Mott R,Platt FMdoi
10.2217/14622416.9.6.717subject
Has Abstractpub_date
2008-06-01 00:00:00pages
717-31issue
6eissn
1462-2416issn
1744-8042journal_volume
9pub_type
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