Related Experiment Video
Updated: Jun 15, 2026
08:22
Assessment and Characterization of Hyaloid Vessels in Mice
Published on: May 15, 2019
The waved with open eyelids (woe) locus is a hypomorphic mouse mutation in Adam17
E L Hassemer1, S M Le Gall, R Liegel
1Department of Cell Biology, Neurobiology and Anatomy, Medical College of Wisconsin, 8701 Watertown Plank, Milwaukee, WI 53226, USA.
Genetics
|March 3, 2010
Summary
The waved with open eyes (woe) mouse mutation reveals a novel Adam17 gene splicing defect, leading to reduced protein function but allowing postnatal survival for developmental studies.
Area of Science:
- Genetics
- Developmental Biology
- Molecular Biology
Background:
- The waved with open eyes (woe) mouse mutation causes wavy fur, eyelids open at birth, and organ enlargement.
- Previous studies confirmed these phenotypes, but a precise molecular cause was unknown.
Purpose of the Study:
- To identify the genetic basis of the woe mutation.
- To characterize the molecular consequences of the mutation on Adam17 protein function.
- To explore the implications for postnatal development and homeostasis.
Main Methods:
- Positional cloning to identify the causative gene and mutation.
- Analysis of Adam17 gene splicing and transcript variants.
- Western blot analysis to assess protein levels and processing.
- Evaluation of Adam17 substrate shedding in mutant mice.
Main Results:
- A C794T substitution in the Adam17 gene was identified, disrupting an exonic splicing enhancer and causing aberrant splicing.
- The predominant woe transcript, Adam17(Delta)(exon7), results in a protein lacking residues 252-281, which is non-functional due to absent prodomain cleavage.
- Residual Adam17 shedding activity originates from a low-level expression of a full-length Adam17 transcript, enabling survival into adulthood.
Conclusions:
- The woe mutation provides a unique model for studying Adam17 function during postnatal development.
- Even minimal functional Adam17 is sufficient for survival, unlike Adam17(-/-) mice that die at birth.
- This study elucidates the critical role of proper Adam17 splicing and function in mammalian development.
Related Concept Videos
02:41Lethal Alleles
Agouti: A Lethal Allele
Lucien Cuénot discovered lethal alleles in 1905 while studying the inheritance of coat color in mice. The agouti gene is responsible for the color of the coat in mice. This gene codes for an agouti-signaling protein, which is responsible for melanin distribution in mammals. The wild-type allele gives rise to gray-brown coat color in mice, while the mutant allele gives rise to yellow coat color. In addition to coat color, the agouti gene is associated with the yellow...
Lucien Cuénot discovered lethal alleles in 1905 while studying the inheritance of coat color in mice. The agouti gene is responsible for the color of the coat in mice. This gene codes for an agouti-signaling protein, which is responsible for melanin distribution in mammals. The wild-type allele gives rise to gray-brown coat color in mice, while the mutant allele gives rise to yellow coat color. In addition to coat color, the agouti gene is associated with the yellow...
01:33Pleiotropy
Pleiotropy is the phenomenon in which a single gene impacts multiple, seemingly unrelated phenotypic traits. For example, defects in the SOX10 gene cause Waardenburg Syndrome Type 4, or WS4, which can cause defects in pigmentation, hearing impairments, and an absence of intestinal contractions necessary for elimination. This diversity of phenotypes results from the expression pattern of SOX10 in early embryonic and fetal development. SOX10 is found in neural crest cells that form melanocytes,...