The waved with open eyelids (woe) locus is a hypomorphic mouse mutation in Adam17. Genetics 2010 May;185(1):245-55
Date
03/03/2010Pubmed ID
20194968Pubmed Central ID
PMC2870960DOI
10.1534/genetics.109.113167Scopus ID
2-s2.0-77956635945 (requires institutional sign-in at Scopus site) 39 CitationsAbstract
The waved with open eyes (woe) locus is a spontaneous recessive mouse mutation that exhibits wavy fur, eyelids open at birth, and enlarged heart and esophagus. In this study, we confirmed the previously identified woe phenotypes and additionally identified anterior eye segment defects, absence of the meibomian glands, and defects in the semilunar cardiac valves. Positional cloning identified a C794T substitution in the Adam17 gene that ablates a putative exonic splicing enhancer (ESE) sequence in exon 7 resulting in aberrant Adam17 splicing. The predominant woe transcript, Adam17(Delta)(exon7), lacks exon 7 resulting in an in-frame deletion of 90 bp and a putative Adam17(Delta252-281) protein lacking residues 252-281 from the metalloprotease domain. Western blot analysis in woe identified only the precursor form of Adam17(Delta252-281) protein. Absence of cleavage of the prodomain renders Adam17(Delta252-281) functionally inactive; however, constitutive and stimulated shedding of Adam17 substrates was detected in woe at significantly reduced levels. This residual Adam17 shedding activity in woe most likely originates from full-length Adam17(T265M) encoded by the Adam17(C794T) transcript identified expressed at severely reduced levels. These results show that even small amounts of functional Adam17 allow woe mice to survive into adulthood. In contrast to Adam17(-/-) mice that die at birth, the viability of woe mice provides an excellent opportunity for studying the role of Adam17 throughout postnatal development and homeostasis.
Author List
Hassemer EL, Le Gall SM, Liegel R, McNally M, Chang B, Zeiss CJ, Dubielzig RD, Horiuchi K, Kimura T, Okada Y, Blobel CP, Sidjanin DJAuthors
Mark T. McNally PhD Associate Professor in the Microbiology and Immunology department at Medical College of WisconsinDanielle Sidjanin Maier PhD Nurse Practitioner in the Medicine department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
ADAM ProteinsADAM17 Protein
Alleles
Alternative Splicing
Amino Acid Sequence
Animals
Base Sequence
Cloning, Molecular
Embryo, Mammalian
Eye
Fibroblasts
Genetic Loci
Mice
Molecular Sequence Data
Mutation
Myocardium
Phenotype
