Mutation in Zeb1 Causes Developmental Issues in Mice
Author Information
Author(s): Kurima Kiyoto, Hertzano Ronna, Gavrilova Oksana, Monahan Kelly, Shpargel Karl B., Nadaraja Garani, Kawashima Yoshiyuki, Lee Kyu Yup, Ito Taku, Higashi Yujiro, Eisenman David J., Strome Scott E., Griffith Andrew J.
Primary Institution: National Institute on Deafness and Other Communication Disorders, National Institutes of Health
Hypothesis
The study aims to identify the causative mutation for the Twirler phenotype in mice.
Conclusion
A noncoding point mutation in the Zeb1 gene leads to multiple developmental malformations and obesity in Twirler mice.
Supporting Evidence
- Heterozygous Tw/+ mice develop obesity and exhibit abnormal behavior.
- Tw/Tw mice have severe malformations and die shortly after birth.
- The identified mutation disrupts a binding site for Myb proteins.
- Knockin mice with the mutation recapitulate the Tw phenotype.
- Zeb1 is expressed at increased levels in Twirler mice compared to wild-type.
- Tw/+ mice show insulin resistance and altered metabolic parameters.
- Histopathological examination revealed no abnormalities in other tissues.
Takeaway
Scientists found a tiny change in a gene that makes some mice have problems with their ears and become overweight.
Methodology
The study involved genetic analysis, phenotypic characterization, and the creation of a knockin mouse model.
Limitations
The study may not fully account for genetic background differences affecting the phenotype.
Participant Demographics
The study involved Twirler mice, specifically heterozygous and homozygous variants.
Statistical Information
P-Value
p<0.0001
Statistical Significance
p<0.05
Digital Object Identifier (DOI)
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