PUBLICATION

DHCR7 links cholesterol synthesis with neuronal development and axonal integrity

Authors
Miyazaki, S., Shimizu, N., Miyahara, H., Teranishi, H., Umeda, R., Yano, S., Shimada, T., Shiraishi, H., Komiya, K., Katoh, A., Yoshimura, A., Hanada, R., Hanada, T.
ID
ZDB-PUB-240417-4
Date
2024
Source
Biochemical and Biophysical Research Communications   712-713: 149932149932 (Journal)
Registered Authors
Hanada, Reiko, Hanada, Toshikatsu
Keywords
Brain, Cholesterol, DHCR7, SLOS, Zebrafish
MeSH Terms
  • Neurons/metabolism
  • Zebrafish*/genetics
  • Zebrafish*/metabolism
  • Animals
  • Lysosomes/metabolism
  • Smith-Lemli-Opitz Syndrome*/genetics
  • Smith-Lemli-Opitz Syndrome*/metabolism
  • Smith-Lemli-Opitz Syndrome*/pathology
  • Oxidoreductases Acting on CH-CH Group Donors/deficiency
  • Oxidoreductases Acting on CH-CH Group Donors/genetics
  • Oxidoreductases Acting on CH-CH Group Donors/metabolism
  • Axons*/metabolism
  • Cholesterol*/metabolism
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism
  • Neurogenesis
  • Autophagy
(all 17)
PubMed
38626530 Full text @ Biochem. Biophys. Res. Commun.
Abstract
The DHCR7 enzyme converts 7-DHC into cholesterol. Mutations in DHCR7 can block cholesterol production, leading to abnormal accumulation of 7-DHC and causing Smith-Lemli-Opitz syndrome (SLOS). SLOS is an autosomal recessive disorder characterized by multiple malformations, including microcephaly, intellectual disability, behavior reminiscent of autism, sleep disturbances, and attention-deficit/hyperactivity disorder (ADHD)-like hyperactivity. Although 7-DHC affects neuronal differentiation in ex vivo experiments, the precise mechanism of SLOS remains unclear. We generated Dhcr7 deficient (dhcr7-/-) zebrafish that exhibited key features of SLOS, including microcephaly, decreased neural stem cell pools, and behavioral phenotypes similar to those of ADHD-like hyperactivity. These zebrafish demonstrated compromised myelination, synaptic anomalies, and neurotransmitter imbalances. The axons of the dhcr7-/- zebrafish showed increased lysosomes and attenuated autophagy, suggesting that autophagy-related neuronal homeostasis is disrupted.
Genes / Markers
Figures
Figure Gallery (4 images)
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Expression
Phenotype
Fish Conditions Stage Phenotype Figure
dhcr7oi14/oi14standard conditionsDays 7-13
dhcr7oi14/oi14standard conditionsDays 30-44
dhcr7oi14/oi14standard conditionsDays 30-44
dhcr7oi14/oi14standard conditionsDays 30-44
dhcr7oi14/oi14standard conditionsDays 30-44
dhcr7oi14/oi14standard conditionsDays 30-44
dhcr7oi14/oi14standard conditionsDays 30-44
dhcr7oi14/oi14standard conditionsDays 45-89
dhcr7oi14/oi14standard conditionsDays 45-89
dhcr7oi14/oi14standard conditionsDays 45-89
1 - 10 of 51
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Mutations / Transgenics
Allele Construct Type Affected Genomic Region
kyu2TgTransgenic Insertion
    nns17TgTransgenic Insertion
      oi14
        		Complex
        oi15
          		MNV
          rw0130aTgTransgenic Insertion
            1 - 5 of 5
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            Human Disease / Model
            Human Disease Fish Conditions Evidence
            Smith-Lemli-Opitz syndromedhcr7oi14/oi14standard conditionsTAS
            1 - 1 of 1
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            Sequence Targeting Reagents
            Target Reagent Reagent Type
            dhcr7CRISPR1-dhcr7CRISPR
            dhcr7CRISPR2-dhcr7CRISPR
            dhcr7CRISPR3-dhcr7CRISPR
            1 - 3 of 3
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            Fish
            Fish
            dhcr7oi14/oi14
            dhcr7oi14/oi14; kyu2Tg/kyu2Tg
            dhcr7oi14/oi14; nns17Tg
            dhcr7oi14/oi14; rw0130aTg
            dhcr7oi15/oi15
            kyu2Tg/kyu2Tg
            nns17Tg
            rw0130aTg
            WT
            1 - 9 of 9
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            Antibodies
            Name Type Antigen Genes Isotypes Host Organism
            Ab1-map1lc3bpolyclonalRabbit
            Ab4-sqstm1polyclonalRabbit
            Ab26-gapdhmonoclonal
              		IgMMouse
              1 - 3 of 3
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              Orthology
              No data available
              Engineered Foreign Genes
              Marker Marker Type Name
              d2EGFPEFGd2EGFP
              KaedeEFGKaede
              TomatoEFGTomato
              1 - 3 of 3
              Show
              Mapping
              No data available
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              Citation
              Miyazaki, S., Shimizu, N., Miyahara, H., Teranishi, H., Umeda, R., Yano, S., Shimada, T., Shiraishi, H., Komiya, K., Katoh, A., Yoshimura, A., Hanada, R., Hanada, T. (2024) DHCR7 links cholesterol synthesis with neuronal development and axonal integrity. Biochemical and Biophysical Research Communications. 712-713:149932149932.