2016
DOI: 10.1186/s12864-016-2679-1
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Whole organism transcriptome analysis of zebrafish models of Bardet-Biedl Syndrome and Alström Syndrome provides mechanistic insight into shared and divergent phenotypes

Abstract: BackgroundBardet-Biedl Syndrome (BBS) and Alström Syndrome are two pleiotropic ciliopathies with significant phenotypic overlap between them across many tissues. Although BBS and Alström genes are necessary for the proper function of primary cilia, their role in defects across multiple organ systems is unclear.MethodsTo provide insight into the pathways underlying BBS and Alström phenotypes, we carried out whole organism transcriptome analysis by RNA sequencing in established zebrafish models of the syndromes.… Show more

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Cited by 15 publications
(21 citation statements)
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“…To better understand how loss of alms1 may impact β-cell function, we generated single-cell homogenates from 5 dpf larvae of either wildtype Tg( insa:mCherry ) or Tg( insa:mCherry ) ;alms1 −/− and isolated the mCherry+ cells via FACS sorting (Fig 5A) (26). Using RNA from the isolated cells, we carried out whole transcriptome analysis via RNA-Seq (26,27). Using a cut-off for differentially expressed genes of a fold change of greater than 1 or less than – 1, we identified a total of 3,880 up-regulated genes and 5,531 down-regulated genes in the alms1 −/− β-cells compared to β-cells isolated from wild type larvae (Fig 5B).…”
Section: Resultsmentioning
confidence: 99%
“…To better understand how loss of alms1 may impact β-cell function, we generated single-cell homogenates from 5 dpf larvae of either wildtype Tg( insa:mCherry ) or Tg( insa:mCherry ) ;alms1 −/− and isolated the mCherry+ cells via FACS sorting (Fig 5A) (26). Using RNA from the isolated cells, we carried out whole transcriptome analysis via RNA-Seq (26,27). Using a cut-off for differentially expressed genes of a fold change of greater than 1 or less than – 1, we identified a total of 3,880 up-regulated genes and 5,531 down-regulated genes in the alms1 −/− β-cells compared to β-cells isolated from wild type larvae (Fig 5B).…”
Section: Resultsmentioning
confidence: 99%
“…Structural data may reveal homologies not detectable at the sequence level, helping to reveal the functions of individual domains. The establishment of zebrafish models of AS [ 80 , 173 ] will facilitate in vivo functional studies, the identification of genetic interactions and therapeutic testing/screening. However, the relatively poor evolutionary conservation of ALMS1 is a limitation of non-mammalian models.…”
Section: Discussionmentioning
confidence: 99%
“…Thus, these data suggest that ALMS1 localises to the nucleus and is important for sustaining the transcriptional activity of RNAPII [ 77 ]. Deficiency of ALMS1 has been associated with altered gene expression profiles in other systems [ 75 , 173 , 174 ]; however, it is unclear if these effects are direct. Of note, the transcriptional program associated with ciliogenesis/confluency was unaffected in Alms1-depleted IMCD3 cells [ 57 ], suggesting that impaired transcription is unlikely to underlie the severe ciliary defects observed in these cells.…”
Section: Alms1 Functionmentioning
confidence: 99%
“…On the other hand, the related phenotype in ALMS model seems UPR unrelated as no upregulation of key players for UPR was observed. Other recent studies suggested that retinopathy in the Alström syndrome might be linked to a defect in the phototransduction cascade (Hostelley et al, 2016). Indeed the related genes were upregulated in embryos of Alms1 mutant zebrafish, while this was not significant in BBS1 mutant zebrafish (Hostelley et al, 2016).…”
Section: Discussionmentioning
confidence: 89%