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 PMID:26371508  

The splicing regulators Esrp1 and Esrp2 direct an epithelial splicing program essential for mammalian development.

Thomas W Bebee | Juw Won Park | Katherine I Sheridan | Claude C Warzecha | Benjamin W Cieply | Alex M Rohacek | Yi Xing | Russ P Carstens
eLife | 2015

Tissue- and cell-type-specific regulators of alternative splicing (AS) are essential components of posttranscriptional gene regulation, necessary for normal cellular function, patterning, and development. Mice with ablation of Epithelial splicing regulatory protein (Esrp1) develop cleft lip and palate. Loss of both Esrp1 and its paralog Esrp2 results in widespread developmental defects with broad implications to human disease. Deletion of the Esrps in the epidermis revealed their requirement for establishing a proper skin barrier, a primary function of epithelial cells comprising the epidermis. We profiled the global Esrp-mediated splicing regulatory program in epidermis, which revealed large-scale programs of epithelial cell-type-specific splicing required for epithelial cell functions. These mice represent a valuable model for evaluating the essential role for AS in development and function of epithelial cells, which play essential roles in tissue homeostasis in numerous organs, and provide a genetic tool to evaluate important functional properties of epithelial-specific splice variants in vivo.

Pubmed ID: 26371508

Associated grants

  • Agency: NIAMS NIH HHS, United States
    Id: R56 AR066741
  • Agency: NIGMS NIH HHS, United States
    Id: R01 GM088342
  • Agency: NIDCR NIH HHS, United States
    Id: R01 DE024749
  • Agency: NIDCR NIH HHS, United States
    Id: R56 DE024749
  • Agency: NIDDK NIH HHS, United States
    Id: P30 DK050306
  • Agency: NIGMS NIH HHS, United States
    Id: R01 GM105431
  • Agency: NIDDK NIH HHS, United States
    Id: T32DK700638
  • Agency: NIGMS NIH HHS, United States
    Id: T32 GM008216
  • Agency: NIAMS NIH HHS, United States
    Id: P30 AR050950
  • Agency: NIGMS NIH HHS, United States
    Id: R01 GM088809
  • Agency: NIDDK NIH HHS, United States
    Id: F32DK098917
  • Agency: NIAMS NIH HHS, United States
    Id: P30 AR057217
  • Agency: NIAMS NIH HHS, United States
    Id: R01 AR066741

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This is a list of tools and resources that we have found mentioned in this publication.


Multivariate Analysis of Transcript Splicing (tool)

RRID:SCR_013049

Software tool to detect differential alternative splicing events from RNA-Seq data. Calculates P value and false discovery rate that difference in isoform ratio of gene between two conditions exceeds given user defined threshold. Can automatically detect and analyze alternative splicing events corresponding to all major types of alternative splicing patterns. Handles replicate RNA-Seq data from both paired and unpaired study design.

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Covance (tool)

RRID:SCR_001224

A contract research organization providing drug development and animal testing services. Under the name Covance Research Products Inc., based in Denver, Pennsylvania, the company also deals in the import, breeding and sale of laboratory animals. It breeds dogs, rabbits, guinea pigs, non-human primates, and pigs, and runs the largest non-human primate laboratory in Germany. (Wikipedia)

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Cuffdiff (tool)

RRID:SCR_001647

Software that estimates expression at transcript-level resolution and controls for variability evident across replicate libraries.

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TopHat (tool)

RRID:SCR_013035

Software tool for fast and high throughput alignment of shotgun cDNA sequencing reads generated by transcriptomics technologies. Fast splice junction mapper for RNA-Seq reads. Aligns RNA-Seq reads to mammalian-sized genomes using ultra high-throughput short read aligner Bowtie, and then analyzes mapping results to identify splice junctions between exons.TopHat2 is accurate alignment of transcriptomes in presence of insertions, deletions and gene fusions.

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ImageQuant (tool)

RRID:SCR_014246

Software for automatic general image analysis. It provides fully automatic analysis of 1-D gels including lane creation, background subtraction, band detection, molecular weight calibration, quantity calibration, and normalization. Editing tools are provided for cropping, rotating, and filtering images.

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Olympus cellSens Software (tool)

RRID:SCR_014551

Software suite for image acquisition and analysis. The software can be paired with high-quality cameras to maximize output quality and export it for sharing and research applications.

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International Mouse Phenotyping Consortium (IMPC) (tool)

RRID:SCR_006158

Center that produces knockout mice and carries out high-throughput phenotyping of each line in order to determine function of every gene in mouse genome. These mice will be preserved in repositories and made available to scientific community representing valuable resource for basic scientific research as well as generating new models for human diseases.

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C57BL/6J (tool)

RRID:IMSR_JAX:000664

Mus musculus with name C57BL/6J from IMSR.

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C57BL/6J (tool)

RRID:IMSR_JAX:000664

Mus musculus with name C57BL/6J from IMSR.

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C57BL/6-Tg(Zp3-cre)93Knw/J (tool)

RRID:IMSR_JAX:003651

Mus musculus with name C57BL/6-Tg(Zp3-cre)93Knw/J from IMSR.

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C57BL/6J (tool)

RRID:IMSR_JAX:000664

Mus musculus with name C57BL/6J from IMSR.

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