Related Experiment Video

Updated: Mar 2, 2026

SorLA and CLC:CLF-1-dependent Downregulation of CNTFRα as Demonstrated by Western Blotting, Inhibition of Lysosomal Enzymes, and Immunocytochemistry
10:16

SorLA and CLC:CLF-1-dependent Downregulation of CNTFRα as Demonstrated by Western Blotting, Inhibition of Lysosomal Enzymes, and Immunocytochemistry

Published on: January 6, 2017

7.7K

Sclt1 deficiency causes cystic kidney by activating ERK and STAT3 signaling

Jianshuang Li1,2, Di Lu2, Huadie Liu2

  • 1Hubei Key Laboratory of Cell Homeostasis, Department of Cell Biology, College of Life Sciences, Wuhan University, Wuhan, Hubei 430072, P.R. China.

Human Molecular Genetics
|May 10, 2017
PubMed

Insights

Researchers developed a new mouse model for Oral-Facial-Digital Syndrome (OFD), a ciliopathy. STAT3 inhibition with pyrimethamine effectively reduced kidney cyst formation in these mice, suggesting a potential treatment.

Area of Science:

  • Genetics and Developmental Biology
  • Cell Biology
  • Medical Genetics

Background:

  • Ciliopathies are inherited disorders caused by defects in cilia structure or function, often leading to complex clinical manifestations.
  • Current treatments for ciliopathies are limited, highlighting the need for new therapeutic strategies and disease models.
  • The Sodium channel and clathrin linker 1 (SCLT1) gene is crucial for ciliogenesis, and its mutations are linked to Oral-Facial-Digital Syndrome (OFD).

Purpose of the Study:

  • To establish and characterize a novel mouse model for SCLT1-associated ciliopathy, specifically OFD.
  • To investigate the cellular and molecular mechanisms underlying the phenotypes observed in the Sclt1 knockout mouse model.
  • To evaluate the therapeutic potential of targeting the STAT3 pathway in mitigating kidney-related ciliopathy phenotypes.

Main Methods:

  • Generation of Sclt1 knockout (Sclt1-/-) mice to model OFD and associated ciliopathies.
  • Phenotypic analysis of Sclt1-/- mice, including assessment of kidney structure, cell proliferation, and apoptosis.
  • Molecular analysis of signaling pathways (PKA, ERK, SMAD, STAT3), inflammation, and fibrosis in affected tissues.
  • Pharmacological intervention using an anti-STAT3 agent (pyrimethamine) to assess its efficacy in reducing kidney cystogenesis.

Main Results:

  • Sclt1-/- mice recapitulated key ciliopathy phenotypes, including cystic kidney, cleft palate, and polydactyly.
  • Loss of Sclt1 led to reduced cilia in the kidney, increased renal tubule epithelial cell proliferation and apoptosis.
  • Activation of pro-inflammatory and pro-fibrotic pathways, along with elevated PKA, ERK, SMAD, and STAT3 signaling, was observed.
  • Treatment with pyrimethamine significantly ameliorated embryonic kidney cyst formation in Sclt1-/- mice.

Conclusions:

  • The Sclt1-/- mouse is a valuable new model for studying OFD and related ciliopathies.
  • STAT3 signaling plays a critical role in the pathogenesis of SCLT1-associated kidney disease.
  • STAT3 inhibition represents a promising therapeutic avenue for treating SCLT1-associated cystic kidney disease.

More Related Videos

Implementing Patch Clamp and Live Fluorescence Microscopy to Monitor Functional Properties of Freshly Isolated PKD Epithelium08:46

Implementing Patch Clamp and Live Fluorescence Microscopy to Monitor Functional Properties of Freshly Isolated PKD Epithelium

Published on: September 1, 2015

10.3K
Skeletal Phenotype Analysis of a Conditional Stat3 Deletion Mouse Model08:42

Skeletal Phenotype Analysis of a Conditional Stat3 Deletion Mouse Model

Published on: July 3, 2020

5.2K

Related Concept Videos

The JAK-STAT Signaling Pathway01:20

The JAK-STAT Signaling Pathway

Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as  SH2...
13.4K
MAPK Signaling Cascades01:07

MAPK Signaling Cascades

Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
8.9K
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a...
5.9K
Role Of Notch Signalling In Intestinal Stem Cell Renewal01:12

Role Of Notch Signalling In Intestinal Stem Cell Renewal

Notch signaling was first discovered in Drosophila melanogaster, where it is involved in cell lineage differentiation. Notch signaling regulates the maintenance and differentiation of intestinal stem cells or ISCs by controlling the expression of atonal homolog 1 or Atoh1. Atoh1 directs cells to differentiate into secretory cells.
Direct cell-to-cell contact is needed for the activation of Notch signaling. The signal is initiated when a notch ligand binds to a receptor on an adjacent cell, also...
2.5K
Notch Signaling Pathway03:14

Notch Signaling Pathway

The Notch signaling pathway is a major intracellular signaling pathway that is highly conserved over a broad spectrum of metazoan species. It stands unique from other intracellular signaling mechanisms in animals because notch protein itself acts as the receptor as well as the primary signaling molecule.
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not...
6.7K
TGF - β Signaling Pathway01:16

TGF - β Signaling Pathway

The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors...
10.8K