Crinkled (Edaradd-cr) Chr13

Crinkled (Edaraddcr), Ectodysplasin-A receptor-associated death domain, Chr. 13, 6.0 cM, Genome Coordinates: 12465936-12466262

The mouse crinkled mutation initially arose spontaneously in 1948 at the Institute of Animal Genetics in Edinburgh, Scotland. There are currently two known spontaneous allelic mutations and one chemically induced mutations of this gene known. Crinkled is one of a group of phenotypic mimics that have long been know in which their phenotypes are essentially identical yet they map to different genes. They were historically known for over 40 years as the tabby mimics or the tabby-crinkled-downless syndrome. It is now know that tabby (Chr. X) is the ligand, ectodysplasin-A, downless (Chr. 10) is the receptor, ectodysplasin-A receptor, and crinkled (Chr. 13), is involved with modulation of the kinetics of interaction between the first two.

Crinkled mutant mice can be identified early from normal mice, around the time of birth, by skin that appears to be thinner than normal. This is due to a lack of large hair follicles. Plucked hairs reveal what appears to be only one of the four hair types, the awl hairs. Two or three of the vibrissae groups are often absent. Pigmentation is less intense due to a delay in hair development. Coccygeal hemivertebrae in mutant mice is manifest clinically as kinks in their tails. Mice develop focal alopecia behind their ears and their tails are completely bald and lack scales or rings. Eyelids may not open completely and corneal opacities may develop. Mutant mice may have small or missing incisors and abnormalities of their molars.

Embyogenesis of hair follicles is delayed in mutant mice. Scanning electron microscopic evaluation of hairs revealed variations in thickness along the long axis (thick and thin regions), twisting, and rough nodular fibers. The tail skin completely lacks the pilosebaceous units which gives it the smooth, hairless appearance at the gross level. Eyelids lack the large modified sebaceous gland known as the Meibomian gland. This gland produces lipid to coat the aqueous secretions from the lacrimal glands and is a critical part of the fluid barrier of the cornea. Many other glands are missing as well as described for the other phenotypic mimics. Neurological lesions may be found in some allelic mutations, which is reflected by changes in neurological lipid types compared to controls. Treatment with epidermal growth factor corrects many of the defects in these mutant mice.

This mouse mutation is a model for some forms of anhydrotic or hypohydrotic ectodermal dysplasia in humans and other species.


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Sofaer JA, Aspects of the tabby-crinkled-downless syndrome. II. Observations on the reaction to changes of genetic background., J Embryol Exp Morphol 1969 Sep;22(2):207-27

Gruneberg H, The glandular aspects of the tabby syndrome in the mouse., J Embryol Exp Morphol 1971 Feb;25(1):1-19

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Keen CL; Hurley LS, Superoxide dismutase activity in the crinkled mutant mouse: ameliorative effects of dietary copper supplementation., Proc Soc Exp Biol Med 1979 Oct;162(1):152-6

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Headon DJ; Emmal SA; Ferguson BM; Tucker AS; Justice MJ; Sharpe PT; Zonana J; Overbeek PA, Gene defect in ectodermal dysplasia implicates a death domain adapter in development., Nature 2001 Dec 20-27;414(6866):913-6

Yan M; Zhang Z; Brady JR; Schilbach S; Fairbrother WJ; Dixit VM, Identification of a Novel Death Domain-Containing Adaptor Molecule for Ectodysplasin-A Receptor that Is Mutated in crinkled Mice., Curr Biol 2002 Mar 5;12(5):409-13

Donahue LR; Marden CC; Coombs H, Edaradd, a remutation to crinkled, MGI Direct Data Submission 2004;():
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