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Updated: Jul 17, 2026
11:05
Behavioral Characterization of an Angelman Syndrome Mouse Model
Published on: October 20, 2023
A hypermorphic mouse Gli3 allele results in a polydactylous limb phenotype
Chengbing Wang1, Yong Pan, Baolin Wang
1Department of Genetic Medicine, Weill Medical College of Cornell University, New York, NY, USA.
Summary
Altering Gli3 protein levels through a novel mutation (Gli3(Delta68)) in mice leads to severe limb digit abnormalities. This genetic modification impacts digit patterning more than previously observed.
Area of Science:
- Developmental biology
- Genetics
- Molecular biology
Background:
- Gli3 protein processing into its repressor form is regulated by proteasomes and inhibited by Hedgehog signaling.
- A concentration gradient of the Gli3 repressor along the anterior-posterior axis of vertebrate limbs is established by restricted Sonic hedgehog expression.
Purpose of the Study:
- To investigate the effects of reduced Gli3 repressor levels and altered full-length Gli3 activity on vertebrate limb development.
- To characterize the limb patterning phenotypes resulting from a specific Gli3 locus deletion (Gli3(Delta68)).
Main Methods:
- Generation of a mouse model with a small deletion at the Gli3 locus (Gli3(Delta68)).
- Analysis of limb development and digit patterning in homozygous and heterozygous Gli3(Delta68) mice.
- Examination of gene expression patterns, including dHand, Hoxd12, Hoxd13, Gli1, and Ptc RNA.
Main Results:
- Homozygous Gli3(Delta68) mice exhibited one to two extra partial anterior digits.
- Mice with one copy of Gli3(Delta68) displayed seven digits and had reduced viability.
- Anterior expansion of dHand, Hoxd12, and Hoxd13 expression was observed without Gli1 or Ptc RNA upregulation.
Conclusions:
- A combined decrease in Gli3 repressor levels and increased full-length Gli3 activity exacerbates digit patterning defects.
- The Gli3(Delta68) mutation provides a model for studying the complex roles of Gli3 processing and activity in limb development.
- These findings highlight the critical balance of Gli3 forms in establishing normal vertebrate limb morphology.
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