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...
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Формат: | Journal article |
Язык: | English |
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2008
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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 |