ZFIN ID: ZDB-FIG-200807-21
Balogh et al., 2020 - Pseudouridylation defect due to DKC1 and NOP10 mutations causes nephrotic syndrome with cataracts, hearing impairment, and enterocolitis. Proceedings of the National Academy of Sciences of the United States of America   117(26):15137-15147 Full text @ Proc. Natl. Acad. Sci. USA
ADDITIONAL FIGURES
EXPRESSION / LABELING:
Genes:
Fish:
Anatomical Terms:
Stage Range: Long-pec to Protruding-mouth
PHENOTYPE:
Fish:
Knockdown Reagent:
Observed In:
Stage Range: Long-pec to Protruding-mouth

Fig. 4 The phenotype of dkc1elu1/elu1 larvae recapitulates the human phenotype. (A) Histological analysis of dkc1elu1/elu1 mutant larvae shows microphthalmia and cataracts. Both the eyes and the optic tectum of the mutants are abnormal and contain a high prevalence of cells with neuroepithelial character. Expression of cell-cycle markers ccnD1 and PH3 in the retinae and the tecta of 2-dpf and 3-dpf larvae, respectively, can be observed throughout these tissues instead of being restricted to the proliferative regions of the ciliary marginal zone and the mediolateral edges, suggesting a defective cell cycle. (All pictures show coronal sections.) (B) Further histological analysis shows 1) deformed semicircular canals, 2) undifferentiated gut, and 3) hypoplastic pronephros with a reduced number of Wt1-positive podocytes in the mutant animals. (Scale bars: 10 μm.) (C) When Dkc1 function is abrogated in Tg(foxd3:EGFP) animals using a synthetic MO oligo, parapineal migration is impaired, and the pineal–parapineal complex appears immature at 3 dpf. (White arrows denote the parapineal.) (D) Markers of tissue differentiation demonstrate a lack of differentiation in the intestines (ifbp), pancreas (try), and the major blood lineages (gata1 and rag1). (Black arrows denote area of expression.) (E) Injection of 1) human WT DKC1 mRNA resulted in phenotypic rescue of the mutant larvae, as shown by the genotyping of larvae showing a WT phenotype. In contrast, injection of 2) human Glu206Lys DKC1 mRNA elicited a much milder rescue, demonstrating the hypomorphic nature of this allele.

Gene Expression Details
Gene Antibody Fish Conditions Stage Anatomy Assay
ccnd1 dkc1elu1/elu1(TU) standard conditions Long-pec retina ISH
Protruding-mouth retina ISH
fabp2 dkc1elu1/elu1(TU) standard conditions Protruding-mouth intestine ISH
gata1a dkc1elu1/elu1(TU) standard conditions Protruding-mouth blood ISH
prss1 dkc1elu1/elu1(TU) standard conditions Protruding-mouth pancreas ISH
rag1 dkc1elu1/elu1(TU) standard conditions Protruding-mouth blood ISH
Antibody Labeling Details No data available
Phenotype Details
Fish Conditions Stage Phenotype
dkc1elu1/elu1(TU) standard conditions Long-pec retina ccnd1 expression increased distribution, abnormal
Long-pec retina ccnd1 expression spatial pattern, abnormal
Protruding-mouth blood gata1a expression decreased amount, abnormal
Protruding-mouth blood rag1 expression decreased amount, abnormal
Protruding-mouth eye decreased size, abnormal
Protruding-mouth gut undifferentiated, abnormal
Protruding-mouth intestine fabp2 expression decreased amount, abnormal
Protruding-mouth lens opaque, abnormal
Protruding-mouth optic tectum morphology, abnormal
Protruding-mouth pancreas prss1 expression decreased amount, abnormal
Protruding-mouth pronephros hypoplastic, abnormal
Protruding-mouth retina ccnd1 expression increased distribution, abnormal
Protruding-mouth retina ccnd1 expression spatial pattern, abnormal
Protruding-mouth semicircular canal deformed, abnormal
zf104Tg + MO2-dkc1 standard conditions Protruding-mouth epiphysis disorganized, abnormal
Protruding-mouth parapineal organ immature, abnormal
Acknowledgments:
ZFIN wishes to thank the journal Proceedings of the National Academy of Sciences of the United States of America for permission to reproduce figures from this article. Please note that this material may be protected by copyright. Full text @ Proc. Natl. Acad. Sci. USA