Differential sensitivity of mouse strains to an N-alkylated imino sugar: glycosphingolipid metabolism and acrosome formation.

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...

Полное описание

Библиографические подробности
Главные авторы: van der Spoel, A, Mott, R, Platt, F
Формат: Journal article
Язык:English
Опубликовано: 2008
_version_ 1826281745376346112
author van der Spoel, A
Mott, R
Platt, F
author_facet van der Spoel, A
Mott, R
Platt, F
author_sort van der Spoel, A
collection OXFORD
description 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.
first_indexed 2024-03-07T00:33:26Z
format Journal article
id oxford-uuid:809b8f72-c071-4f11-a051-16d49d933b41
institution University of Oxford
language English
last_indexed 2024-03-07T00:33:26Z
publishDate 2008
record_format dspace
spelling oxford-uuid:809b8f72-c071-4f11-a051-16d49d933b412022-03-26T21:24:20ZDifferential sensitivity of mouse strains to an N-alkylated imino sugar: glycosphingolipid metabolism and acrosome formation.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:809b8f72-c071-4f11-a051-16d49d933b41EnglishSymplectic Elements at Oxford2008van der Spoel, AMott, RPlatt, FThis 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.
spellingShingle van der Spoel, A
Mott, R
Platt, F
Differential sensitivity of mouse strains to an N-alkylated imino sugar: glycosphingolipid metabolism and acrosome formation.
title Differential sensitivity of mouse strains to an N-alkylated imino sugar: glycosphingolipid metabolism and acrosome formation.
title_full Differential sensitivity of mouse strains to an N-alkylated imino sugar: glycosphingolipid metabolism and acrosome formation.
title_fullStr Differential sensitivity of mouse strains to an N-alkylated imino sugar: glycosphingolipid metabolism and acrosome formation.
title_full_unstemmed Differential sensitivity of mouse strains to an N-alkylated imino sugar: glycosphingolipid metabolism and acrosome formation.
title_short Differential sensitivity of mouse strains to an N-alkylated imino sugar: glycosphingolipid metabolism and acrosome formation.
title_sort differential sensitivity of mouse strains to an n alkylated imino sugar glycosphingolipid metabolism and acrosome formation
work_keys_str_mv AT vanderspoela differentialsensitivityofmousestrainstoannalkylatediminosugarglycosphingolipidmetabolismandacrosomeformation
AT mottr differentialsensitivityofmousestrainstoannalkylatediminosugarglycosphingolipidmetabolismandacrosomeformation
AT plattf differentialsensitivityofmousestrainstoannalkylatediminosugarglycosphingolipidmetabolismandacrosomeformation