Hair and skin sterols in normal mice and those with deficient dehydrosterol reductase (DHCR7), the enzyme associated with Smith-Lemli-Opitz syndrome

Research output: Contribution to journalArticle

Standard

Harvard

APA

Vancouver

Author

Bibtex

@article{96e0e45740094212a7329a2ba619139a,
title = "Hair and skin sterols in normal mice and those with deficient dehydrosterol reductase (DHCR7), the enzyme associated with Smith-Lemli-Opitz syndrome",
abstract = "Our recent studies have focused on cholesterol synthesis in mouse models for 7-dehydrosterolreductase (DHCR7) deficiency, also known as Smith-Lemli-Opitz syndrome. Investigations of such mutants have relied on tissue and blood levels of the cholesterol precursor 7-dehydrocholesterol (7DHC) and its 8-dehydro isomer. In this investigation by gas chromatography/mass spectrometry (GC/MS) we have identified and quantified cholesterol and its precursors (7DHC, desmosterol, lathosterol, lanosterol and cholest-7,24-dien-3β-ol) in mouse hair. The components were characterized and their concentrations were compared to those found in mouse skin and serum. Hair appeared unique in that desmosterol was a major sterol component, almost matching in concentration cholesterol itself. In DHCR7 deficient mice, dehydrodesmosterol (DHD) was the dominant hair Δ(7) sterol. Mutant mouse hair had much higher concentrations of 7-dehydrosterols relative to cholesterol than did serum or tissue at all ages studied. The 7DHC/C ratio in hair was typically about sevenfold the value in serum or skin and the DHD/D ratio was 100× that of the serum 7DHC/C ratio. Mutant mice compensate for their DHCR7 deficiency with maturity, and the tissue and blood 7DHC/C become close to normal. That hair retains high relative concentrations of the dehydro precursors suggests that the apparent up-regulation of Dhcr7 seen in liver is slower to develop at the site of hair cholesterol synthesis.",
keywords = "Smith-Lemli-Opitz syndrome (SLOS), Cholesterol biosynthesis, Sterol GC/MS, DHCR7 deficiency, Hair sterols",
author = "M Serra and X Matabosch and L Ying and G Watson and Cedric Shackleton",
year = "2010",
month = nov,
day = "1",
doi = "10.1016/j.jsbmb.2010.08.006",
language = "English",
volume = "122",
pages = "318--25",
journal = "The Journal of Steroid Biochemistry and Molecular Biology",
issn = "0960-0760",
publisher = "Elsevier",
number = "5",

}

RIS

TY - JOUR

T1 - Hair and skin sterols in normal mice and those with deficient dehydrosterol reductase (DHCR7), the enzyme associated with Smith-Lemli-Opitz syndrome

AU - Serra, M

AU - Matabosch, X

AU - Ying, L

AU - Watson, G

AU - Shackleton, Cedric

PY - 2010/11/1

Y1 - 2010/11/1

N2 - Our recent studies have focused on cholesterol synthesis in mouse models for 7-dehydrosterolreductase (DHCR7) deficiency, also known as Smith-Lemli-Opitz syndrome. Investigations of such mutants have relied on tissue and blood levels of the cholesterol precursor 7-dehydrocholesterol (7DHC) and its 8-dehydro isomer. In this investigation by gas chromatography/mass spectrometry (GC/MS) we have identified and quantified cholesterol and its precursors (7DHC, desmosterol, lathosterol, lanosterol and cholest-7,24-dien-3β-ol) in mouse hair. The components were characterized and their concentrations were compared to those found in mouse skin and serum. Hair appeared unique in that desmosterol was a major sterol component, almost matching in concentration cholesterol itself. In DHCR7 deficient mice, dehydrodesmosterol (DHD) was the dominant hair Δ(7) sterol. Mutant mouse hair had much higher concentrations of 7-dehydrosterols relative to cholesterol than did serum or tissue at all ages studied. The 7DHC/C ratio in hair was typically about sevenfold the value in serum or skin and the DHD/D ratio was 100× that of the serum 7DHC/C ratio. Mutant mice compensate for their DHCR7 deficiency with maturity, and the tissue and blood 7DHC/C become close to normal. That hair retains high relative concentrations of the dehydro precursors suggests that the apparent up-regulation of Dhcr7 seen in liver is slower to develop at the site of hair cholesterol synthesis.

AB - Our recent studies have focused on cholesterol synthesis in mouse models for 7-dehydrosterolreductase (DHCR7) deficiency, also known as Smith-Lemli-Opitz syndrome. Investigations of such mutants have relied on tissue and blood levels of the cholesterol precursor 7-dehydrocholesterol (7DHC) and its 8-dehydro isomer. In this investigation by gas chromatography/mass spectrometry (GC/MS) we have identified and quantified cholesterol and its precursors (7DHC, desmosterol, lathosterol, lanosterol and cholest-7,24-dien-3β-ol) in mouse hair. The components were characterized and their concentrations were compared to those found in mouse skin and serum. Hair appeared unique in that desmosterol was a major sterol component, almost matching in concentration cholesterol itself. In DHCR7 deficient mice, dehydrodesmosterol (DHD) was the dominant hair Δ(7) sterol. Mutant mouse hair had much higher concentrations of 7-dehydrosterols relative to cholesterol than did serum or tissue at all ages studied. The 7DHC/C ratio in hair was typically about sevenfold the value in serum or skin and the DHD/D ratio was 100× that of the serum 7DHC/C ratio. Mutant mice compensate for their DHCR7 deficiency with maturity, and the tissue and blood 7DHC/C become close to normal. That hair retains high relative concentrations of the dehydro precursors suggests that the apparent up-regulation of Dhcr7 seen in liver is slower to develop at the site of hair cholesterol synthesis.

KW - Smith-Lemli-Opitz syndrome (SLOS)

KW - Cholesterol biosynthesis

KW - Sterol GC/MS

KW - DHCR7 deficiency

KW - Hair sterols

U2 - 10.1016/j.jsbmb.2010.08.006

DO - 10.1016/j.jsbmb.2010.08.006

M3 - Article

C2 - 20804844

VL - 122

SP - 318

EP - 325

JO - The Journal of Steroid Biochemistry and Molecular Biology

JF - The Journal of Steroid Biochemistry and Molecular Biology

SN - 0960-0760

IS - 5

ER -