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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Aug 08, 2022 |
| Title |
X-linked myotubular myopathy is associated with epigenetic alterations and is ameliorated by HDAC inhibition |
| Organisms |
Danio rerio; Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
X-linked myotubular myopathy (XLMTM) is a fatal neuromuscular disorder caused by loss of function mutations in MTM1 . At present, there are no directed therapies for XLMTM, and incomplete understanding of disease pathomechanisms. To address these knowledge gaps, we performed a drug screen in mtm1 mutant zebrafish andidentified four positive hits, including valproic acid, which functions as a potent suppressor of the mtm1 zebrafish phenotype via HDAC inhibition. We translated these findings to a mouse XLMTM model, and showed that valproic acid ameliorates the murine phenotype.
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| Overall design |
Zebrafish: At 1 dpf, embryos from single-pair in-crossings of mtm1+/zf711 adults were divided equally into three chemical treatment groups: DMSO, sodium valproate (VPA), or trichostatin A. For tissue collection, the posterior section of larvae and fin fold tissues was dissected and snap frozen on dry ice at 4 dpf. A total of n=6-10 larvae per pool per condition with 5 biological replicates were used for RNA extraction. Mice: Bulk RNA sequencing was performed on RNA extracts from tibialis anterior muscle from 35 day old Mtm1KO and WT mice, either treated with PBS or valproic acid (VPA) starting at 21 days.
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| Contributor(s) |
Volpatti J, Ghahramani Seno MM, Mansat M, Sabha N, Sarikaya E, Goodman S, Chater-Diehl E, Celik A, Pannia E, Froment C, Combes-Soia L, Maani N, Yuki K, Chicanne G, Uusküla-Reimand L, Monis S, Alvi S, Genetti C, Payrastre B, Beggs A, Bonnemann C, Muntoni F, Wilson M, Weksberg R, Viaud J, Dowling JJ |
| Citation(s) |
35844027 |
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| Submission date |
Aug 05, 2022 |
| Last update date |
Nov 07, 2022 |
| Contact name |
James J Dowling |
| E-mail(s) |
James.dowling@sickkids.ca
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| Organization name |
Hospital for Sick Children
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| Street address |
686 Bay Street
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| City |
Toronto |
| State/province |
Ontario |
| ZIP/Postal code |
M5G 0A4 |
| Country |
Canada |
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| Platforms (2) |
| GPL17021 |
Illumina HiSeq 2500 (Mus musculus) |
| GPL18413 |
Illumina HiSeq 2500 (Danio rerio) |
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| Samples (49)
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| GSM6433968 |
Mtm1 KO, VPA treatment, mouse, rep4 |
| GSM6433969 |
WT, VPA treatment, mouse, rep1 |
| GSM6433970 |
WT, VPA treatment, mouse, rep2 |
| GSM6433971 |
WT, VPA treatment, mouse, rep3 |
| GSM6433972 |
WT, VPA treatment, mouse, rep4 |
| GSM6433973 |
Mtm1 KO, PBS treatment, mouse, rep1 |
| GSM6433974 |
Mtm1 KO, PBS treatment, mouse, rep2 |
| GSM6433975 |
Mtm1 KO, PBS treatment, mouse, rep3 |
| GSM6433976 |
Mtm1 KO, PBS treatment, mouse, rep4 |
| GSM6433977 |
WT, PBS treatment, mouse, rep1 |
| GSM6433978 |
WT, PBS treatment, mouse, rep2 |
| GSM6433979 |
WT, PBS treatment, mouse, rep3 |
| GSM6433980 |
WT, PBS treatment, mouse, rep4 |
| GSM6433981 |
WT, DMSO treatment, zebrafish, rep1 |
| GSM6433982 |
WT, DMSO treatment, zebrafish, rep2 |
| GSM6433983 |
WT, DMSO treatment, zebrafish, rep3 |
| GSM6433984 |
WT, DMSO treatment, zebrafish, rep4 |
| GSM6433985 |
WT, DMSO treatment, zebrafish, rep5 |
| GSM6433986 |
HET, TSA treatment, zebrafish, rep1 |
| GSM6433987 |
HET, TSA treatment, zebrafish, rep2 |
| GSM6433988 |
HET, TSA treatment, zebrafish, rep3 |
| GSM6433989 |
HET, TSA treatment, zebrafish, rep4 |
| GSM6433990 |
Mtm1 KO, TSA treatment, zebrafish, rep1 |
| GSM6433991 |
Mtm1 KO, TSA treatment, zebrafish, rep2 |
| GSM6433992 |
Mtm1 KO, TSA treatment, zebrafish, rep3 |
| GSM6433993 |
Mtm1 KO, TSA treatment, zebrafish, rep4 |
| GSM6433994 |
Mtm1 KO, TSA treatment, zebrafish, rep5 |
| GSM6433995 |
HET, VPA treatment, zebrafish, rep1 |
| GSM6433996 |
HET, VPA treatment, zebrafish, rep2 |
| GSM6433997 |
HET, VPA treatment, zebrafish, rep3 |
| GSM6433998 |
HET, VPA treatment, zebrafish, rep4 |
| GSM6433999 |
HET, VPA treatment, zebrafish, rep5 |
| GSM6434000 |
Mtm1 KO, VPA treatment, zebrafish, rep1 |
| GSM6434001 |
Mtm1 KO, VPA treatment, zebrafish, rep2 |
| GSM6434002 |
Mtm1 KO, VPA treatment, zebrafish, rep3 |
| GSM6434003 |
Mtm1 KO, VPA treatment, zebrafish, rep4 |
| GSM6434004 |
Mtm1 KO, VPA treatment, zebrafish, rep5 |
| GSM6434005 |
HET, DMSO treatment, zebrafish, rep1 |
| GSM6434006 |
HET, DMSO treatment, zebrafish, rep2 |
| GSM6434007 |
HET, DMSO treatment, zebrafish, rep3 |
| GSM6434008 |
HET, DMSO treatment, zebrafish, rep4 |
| GSM6434009 |
HET, DMSO treatment, zebrafish, rep5 |
| GSM6434010 |
Mtm1 KO, DMSO treatment, zebrafish, rep1 |
| GSM6434011 |
Mtm1 KO, DMSO treatment, zebrafish, rep2 |
| GSM6434012 |
Mtm1 KO, DMSO treatment, zebrafish, rep3 |
| GSM6434013 |
Mtm1 KO, DMSO treatment, zebrafish, rep4 |
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| Relations |
| BioProject |
PRJNA866536 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE210642_Mice_raw_count.tsv.gz |
852.0 Kb |
(ftp)(http) |
TSV |
| GSE210642_zebrafish_raw_count.tsv.gz |
916.5 Kb |
(ftp)(http) |
TSV |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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