Differential regulation of the human <i>CYP11A1</i> promoter in mouse brain and adrenals

Chiang, Yen-Feng; Lin, Hui-Ting; Hu, Jiwei; Tai, Y. T.; Lin, Yu‐Chi; Hu, Meng Chun

doi:10.1002/jcp.22534

Cited by 12 publications

(6 citation statements)

References 44 publications

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“…Cyp3a11 is, however, predominantly expressed in cortex (55). CYP11A1 is the cholesterol 22R-hydroxylase required for neurosteroid biosynthesis and has been shown to be expressed in mouse brain (65). It first hydroxylates cholesterol at position C-22R, then at C-20, then cleaves the bond between these two carbons to generate pregnenolone.…”

Section: Discussionmentioning

confidence: 99%

Localization of sterols and oxysterols in mouse brain reveals distinct spatial cholesterol metabolism

Yutuc

Angelini

Baumert

et al. 2020

Proc. Natl. Acad. Sci. U.S.A.

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Dysregulated cholesterol metabolism is implicated in a number of neurological disorders. Many sterols, including cholesterol and its precursors and metabolites, are biologically active and important for proper brain function. However, spatial cholesterol metabolism in brain and the resulting sterol distributions are poorly defined. To better understand cholesterol metabolism in situ across the complex functional regions of brain, we have developed on-tissue enzyme-assisted derivatization in combination with microliquid extraction for surface analysis and liquid chromatography-mass spectrometry to locate sterols in tissue slices (10 µm) of mouse brain. The method provides sterolomic analysis at 400-µm spot diameter with a limit of quantification of 0.01 ng/mm2. It overcomes the limitations of previous mass spectrometry imaging techniques in analysis of low-abundance and difficult-to-ionize sterol molecules, allowing isomer differentiation and structure identification. Here we demonstrate the spatial distribution and quantification of multiple sterols involved in cholesterol metabolic pathways in wild-type andcholesterol 24S-hydroxylaseknockout mouse brain. The technology described provides a powerful tool for future studies of spatial cholesterol metabolism in healthy and diseased tissues.

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Section: Discussionmentioning

confidence: 99%

Localization of sterols and oxysterols in mouse brain reveals distinct spatial cholesterol metabolism

Yutuc

Angelini

Baumert

et al. 2020

Proc. Natl. Acad. Sci. U.S.A.

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“…The xenobiotic-metabolizing P450 enzymes, such as CYP11A1 , play a central role in the oxidative metabolism of a wide variety of endogenous and exogenous compounds including environmental carcinogens, plant toxins, and a wide range of pharmaceuticals (Gonzalez and Gelboin, 1994; Gut et al, 2000; Huang et al, 2000). CYP11A1 mRNA and protein have been found in several regions of the nervous system including the cerebellum, retina, and hippocampus; however, the transcriptional regulation and cellular and anatomical distribution of CYP11A1 in the brain have not been clearly determined (Wu et al, 2007; Chiang et al, 2011). …”

Section: Discussionmentioning

confidence: 99%

Assessment of gene expression in peripheral blood using RNAseq before and after weight restoration in anorexia nervosa

Kim

Trace

Crowley

et al. 2013

Psychiatry Research

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We examined gene expression in the blood of six females with anorexia nervosa (AN) before and after weight restoration using RNAseq. AN cases (aged 19-39) completed clinical assessments and had blood drawn for RNA at hospital admission (T1, < ~75% ideal body weight, IBW) and again at discharge (T2, ≥ ~85% IBW). To examine the relationship between weight restoration and differential gene expression, normalized gene expression levels were analyzed using a paired design. We found 564 genes whose expression was nominally significantly different following weight restoration (p < 0.01, 231 increased and 333 decreased). With a more stringent significance threshold (false discovery rate q < 0.05), 67 genes met criteria for differential expression. Of the top 20 genes, CYP11A1, C16orf11, LINC00235, and CPA3 were down-regulated more than two-fold after weight restoration while multiple olfactory receptor genes (OR52J3, OR51L1, OR51A4, OR51A2) were up-regulated more than two-fold after weight restoration. Pathway analysis revealed up-regulation of two broad pathways with largely overlapping genes, one related to protein secretion and signaling and the other associated with defense response to bacterial regulation. Although results are preliminary secondary to a small sample size, these data provide initial evidence of transcriptional alterations during weight restoration in AN.

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“…Whilst the resultant expression of Cre Recombinase (as defined by lineage tracing) closely mimics that of the Cyp11a1-GC mouse, there are several distinct differences. Expression of SCC-Cre is detected albeit weakly in the fetal ovary (endogenous Cyp11a1 is not found in the fetal ovary), and in distinct regions of the brain in both fetal and adult life, conversely no fetal ovary expression is detected in the Cyp11a1-GC line, and expression in the brain is restricted to postnatal life, and in the hindbrain, a localisation distinct to that of expression in the SCC-Cre brain [17], [18].…”

Section: Discussionmentioning

confidence: 89%

Targeting of GFP-Cre to the Mouse Cyp11a1 Locus Both Drives Cre Recombinase Expression in Steroidogenic Cells and Permits Generation of Cyp11a1 Knock Out Mice

et al. 2014

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To permit conditional gene targeting of floxed alleles in steroidogenic cell-types we have generated a transgenic mouse line that expresses Cre Recombinase under the regulation of the endogenous Cytochrome P450 side chain cleavage enzyme (Cyp11a1) promoter. Mice Carrying the Cyp11a1-GC (GFP-Cre) allele express Cre Recombinase in fetal adrenal and testis, and adrenal cortex, testicular Leydig cells (and a small proportion of Sertoli cells), theca cells of the ovary, and the hindbrain in postnatal life. Circulating testosterone concentration is unchanged in Cyp11+/GC males, suggesting steroidogenesis is unaffected by loss of one allele of Cyp11a1, mice are grossly normal, and Cre Recombinase functions to recombine floxed alleles of both a YFP reporter gene and the Androgen Receptor (AR) in steroidogenic cells of the testis, ovary, adrenal and hindbrain. Additionally, when bred to homozygosity (Cyp11a1GC/GC), knock-in of GFP-Cre to the endogenous Cyp11a1 locus results in a novel mouse model lacking endogenous Cyp11a1 (P450-SCC) function. This unique dual-purpose model has utility both for those wishing to conditionally target genes within steroidogenic cell types and for studies requiring mice lacking endogenous steroid hormone production.

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Differential regulation of the human CYP11A1 promoter in mouse brain and adrenals

Cited by 12 publications

References 44 publications

Localization of sterols and oxysterols in mouse brain reveals distinct spatial cholesterol metabolism

Localization of sterols and oxysterols in mouse brain reveals distinct spatial cholesterol metabolism

Assessment of gene expression in peripheral blood using RNAseq before and after weight restoration in anorexia nervosa

Targeting of GFP-Cre to the Mouse Cyp11a1 Locus Both Drives Cre Recombinase Expression in Steroidogenic Cells and Permits Generation of Cyp11a1 Knock Out Mice

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