Analysis by liquid chromatography-mass spectrometry of sterols and oxysterols in brain of the newborn Dhcr7(Δ3-5/T93M) mouse: a model of Smith-Lemli-Opitz syndrome

Anna Meljon; Gordon L Watson; Yuqin Wang; Cedric H L Shackleton; William J Griffiths

doi:10.1016/j.bcp.2013.03.003

Analysis by liquid chromatography-mass spectrometry of sterols and oxysterols in brain of the newborn Dhcr7(Δ3-5/T93M) mouse: a model of Smith-Lemli-Opitz syndrome

Anna Meljon, Gordon L Watson, Yuqin Wang, Cedric H L Shackleton, William J Griffiths

Research output: Contribution to journal › Article › peer-review

22 Citations (Scopus)

Abstract

In this study the sterol and oxysterol profile of newborn brain from the Dhcr7(Δ3-5/T93M) mouse model of Smith-Lemli-Opitz syndrome (SLOS) has been investigated. This is a viable mouse model which is compound heterozygous containing one null allele and one T93M mutation on Dhcr7. We find the SLOS mouse has reduced levels of cholesterol and desmosterol and increased levels of 7- and 8-dehydrocholesterol and of 7- and 8-dehydrodesmosterol in brain compared to the wild type. The profile of enzymatically formed oxysterols in the SLOS mouse resembles that in the wild type but the level of 24S-hydroxycholesterol, the dominating cholesterol metabolite, is reduced in a similar proportion to that of cholesterol. A number of oxysterols abundant in the SLOS mouse are probably derived from 7-dehydrocholesterol, however, the mechanism of their formation is unclear.

Original language	English
Pages (from-to)	43-55
Number of pages	13
Journal	Biochemical Pharmacology
Volume	86
Issue number	1
DOIs	https://doi.org/10.1016/j.bcp.2013.03.003
Publication status	Published - 01 Jul 2013
Externally published	Yes

Bibliographical note

Keywords

Animals
Animals, Newborn
Cholesterol/metabolism
Chromatography, Liquid
Desmosterol/metabolism
Gene Knock-In Techniques
Mice
Mice, Mutant Strains
Oxidation-Reduction
Oxidoreductases Acting on CH-CH Group Donors/genetics
Smith-Lemli-Opitz Syndrome/genetics
Spectrometry, Mass, Electrospray Ionization
Sterols/metabolism

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title = "Analysis by liquid chromatography-mass spectrometry of sterols and oxysterols in brain of the newborn Dhcr7(Δ3-5/T93M) mouse: a model of Smith-Lemli-Opitz syndrome",

abstract = "In this study the sterol and oxysterol profile of newborn brain from the Dhcr7(Δ3-5/T93M) mouse model of Smith-Lemli-Opitz syndrome (SLOS) has been investigated. This is a viable mouse model which is compound heterozygous containing one null allele and one T93M mutation on Dhcr7. We find the SLOS mouse has reduced levels of cholesterol and desmosterol and increased levels of 7- and 8-dehydrocholesterol and of 7- and 8-dehydrodesmosterol in brain compared to the wild type. The profile of enzymatically formed oxysterols in the SLOS mouse resembles that in the wild type but the level of 24S-hydroxycholesterol, the dominating cholesterol metabolite, is reduced in a similar proportion to that of cholesterol. A number of oxysterols abundant in the SLOS mouse are probably derived from 7-dehydrocholesterol, however, the mechanism of their formation is unclear.",

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author = "Anna Meljon and Watson, {Gordon L} and Yuqin Wang and Shackleton, {Cedric H L} and Griffiths, {William J}",

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AU - Watson, Gordon L

AU - Wang, Yuqin

AU - Shackleton, Cedric H L

AU - Griffiths, William J

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KW - Desmosterol/metabolism

KW - Gene Knock-In Techniques

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KW - Mice, Mutant Strains

KW - Oxidation-Reduction

KW - Oxidoreductases Acting on CH-CH Group Donors/genetics

KW - Smith-Lemli-Opitz Syndrome/genetics

KW - Spectrometry, Mass, Electrospray Ionization

KW - Sterols/metabolism

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SN - 0006-2952

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Analysis by liquid chromatography-mass spectrometry of sterols and oxysterols in brain of the newborn Dhcr7(Δ3-5/T93M) mouse: a model of Smith-Lemli-Opitz syndrome

Abstract

Bibliographical note

Keywords

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