Related Experiment Video

Updated: May 31, 2025

Methods for Evaluating the Role of c-Fos and Dusp1 in Oncogene Dependence
10:09

Methods for Evaluating the Role of c-Fos and Dusp1 in Oncogene Dependence

Published on: January 7, 2019

8.2K

Independent genetic strategies define the scope and limits of CDKL5 deficiency disorder reversal

Xie Song1, Zijie Xia2, Dayne Martinez2

  • 1Department of Genetics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19102, USA; Department of Hepatobiliary Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong 250000, China.

Cell Reports. Medicine
|January 24, 2025
PubMed

Insights

Re-expressing the CDKL5 gene in mouse models of Cyclin-dependent kinase-like 5 (CDKL5) deficiency disorder (CDD) can reverse symptoms. Early intervention is most effective, especially in females, highlighting age and disease stage importance for CDD treatments.

Area of Science:

  • Neuroscience
  • Genetics
  • Developmental Biology

Background:

  • Cyclin-dependent kinase-like 5 (CDKL5) deficiency disorder (CDD) is a severe neurodevelopmental syndrome.
  • Mutations in the X-linked CDKL5 gene cause CDD, impacting brain development.
  • CDKL5 is crucial during development, but its role post-development is less understood.

Purpose of the Study:

  • To investigate the efficacy of CDKL5 re-expression in reversing CDD phenotypes.
  • To compare treatment effects across different ages and sexes in mouse models.
  • To determine the optimal timing for therapeutic intervention in CDD.

Main Methods:

  • Utilized two independent mouse models of CDKL5 deficiency disorder.
  • Systematically compared phenotype reversal following endogenous Cdkl5 re-activation.
  • Assessed outcomes across various ages and in both male and female mice.
  • Evaluated effects on motor function, seizures, and cognitive abilities.

Main Results:

  • Early re-activation of CDKL5 in heterozygous female mice reversed most CDD-related phenotypes, excluding working memory deficits.
  • Later re-expression showed benefits for some traits but had limited impact on cognitive function.
  • Seizure prevention was significantly more effective with early intervention in females, with reduced efficacy after seizure onset.
  • Phenotype reversal potential was demonstrated in both sexes, though timing was critical.

Conclusions:

  • Endogenous CDKL5 re-expression shows significant therapeutic potential for CDD across both sexes.
  • The age of intervention and disease stage critically influence treatment outcomes.
  • These findings have implications for designing age- and stage-specific clinical trials for CDD.
Keywords:
CDDCDKL5 deficiency disorderbehavioral phenotypeclinical trial designepilepsygenetic reversallearning and memorymouse model

More Related Videos

Engineering Oncogenic Heterozygous Gain-of-Function Mutations in Human Hematopoietic Stem and Progenitor Cells12:04

Engineering Oncogenic Heterozygous Gain-of-Function Mutations in Human Hematopoietic Stem and Progenitor Cells

Published on: March 10, 2023

3.4K
Genome Editing and Directed Differentiation of hPSCs for Interrogating Lineage Determinants in Human Pancreatic Development09:37

Genome Editing and Directed Differentiation of hPSCs for Interrogating Lineage Determinants in Human Pancreatic Development

Published on: March 5, 2017

13.1K

Related Concept Videos

Conservative Site-specific Recombination and Phase Variation02:53

Conservative Site-specific Recombination and Phase Variation

Because the DNA segments are cut and reorganized in a direction-specific manner, site-specific recombination has emerged as an efficient genetic engineering technique. Flippase and Cyclization recombinases or Flp and Cre, respectively, are two members of the tyrosine recombinase family derived from bacteriophages, that are used to mediate site-specific DNA insertions, deletions, and targeted expression of proteins in mammalian cell lines.
The recognition sites for Cre recombinase called LoxP...
5.9K
M-Cdk Drives Transition Into Mitosis02:15

M-Cdk Drives Transition Into Mitosis

Checkpoints throughout the cell cycle serve as safeguards and gatekeepers, allowing the cell cycle to progress in favorable conditions and slow or halt it in problematic ones. This regulation is known as the cell cycle control system.
Cyclin-dependent kinases, or Cdks, work in concert with cyclins to control cell cycle transitions. M-Cdk, a complex of Cdk1 bound to M cyclin, is a well-known example of this coordinated control that drives the transition from the G2 to the M phase.
M cyclin...
5.5K
Inhibition of Cdk Activity02:34

Inhibition of Cdk Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
4.6K
In-vitro Mutagenesis01:16

In-vitro Mutagenesis

To learn more about the function of a gene, researchers can observe what happens when the gene is inactivated or “knocked out,” by creating genetically engineered knockout animals. Knockout mice have been particularly useful as models for human diseases such as cancer, Parkinson’s disease, and diabetes.
13.7K