Skinbase
Mouse Skin and Hair Database
Downless (Edar-dl) Chr10
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_Chr10/001_B6C3Fe-dlJ_retroaural_skin_no_follicles_index_TMB.jpg)
Retroaural skin from an adult downless mutant mouse lacks pilosebaceous units resulting in a halo around the areas without hair.
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_Chr10/002_B6C3Fe-dlJ_mut_eyelid_no_meibomian_glands_index_TMB.jpg)
Eyelid from a downless mutant mouse has large cilia (hair follicles that form eyelashes) but lacks the Meibomian gland.
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_Chr10/003_B6C3Fe-dlJ_tailskin_no_hair_follicles_index_TMB.jpg)
Tail skin from a downless mutant mouse lacks all pilosebaceous untils (no hair follicles and their associated sebaceous glands). This gives the tail skin a flat appearance with the dermis devoid of adnexal structures. The epidermis of tail skin is thicker than truncal skin normally and is more cornified.
_Chr10/001_B6C3Fe-dlJ_retroaural_skin_no_follicles_index.jpg)
_Chr10/002_B6C3Fe-dlJ_mut_eyelid_no_meibomian_glands_index.jpg)
_Chr10/003_B6C3Fe-dlJ_tailskin_no_hair_follicles_index.jpg)
Downless (Edardl), Ectodysplasin-A receptor, Chr. 10, 29.0 cM, Genome Coordinates: 58350589-58425509
The mouse downless mutation initially arose spontaneously in the late 1950s on the A/H strain. There are currently 5 known allelic mutations. Downless 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.
Downless mutant mice are very similar to tabby and crinkled mice. Mutant mice have thin, shiny hair coats with areas of alopecia, notably behind the ears and on the tail. The tail skin completely lacks the pilosebaceous units which gives it the smooth, hairless appearance at the gross level. The trunk has only awl hairs. Abnormalities of the teeth include missing or malformed incisors and molars. Eyelids may not open completely and corneal opacities may develop. 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.
This mouse mutation is a model for some forms of anhydrotic or hypohydrotic ectodermal dysplasia in humans and other species.
The mouse downless mutation initially arose spontaneously in the late 1950s on the A/H strain. There are currently 5 known allelic mutations. Downless 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.
Downless mutant mice are very similar to tabby and crinkled mice. Mutant mice have thin, shiny hair coats with areas of alopecia, notably behind the ears and on the tail. The tail skin completely lacks the pilosebaceous units which gives it the smooth, hairless appearance at the gross level. The trunk has only awl hairs. Abnormalities of the teeth include missing or malformed incisors and molars. Eyelids may not open completely and corneal opacities may develop. 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.
This mouse mutation is a model for some forms of anhydrotic or hypohydrotic ectodermal dysplasia in humans and other species.
References
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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
Sofaer JA, Hair follicle initiation in reciprocal recombinations of downless homozygote and heterozygote mouse tail epidermis and dermis., Dev Biol 1973 Oct;34(2):289-96
Sofaer JA, Differences between tabby and downless mouse epidermis and dermis in culture., Genet Res 1974 Apr;23(2):219-25
Cattanach BM, Dl<slk> - sleek, Mouse News Lett 1975;53():29
Green MC; Sweet HO, Chromosome 10., Mouse News Lett 1975;53():34
Sofaer JA, The teeth of the sleek mouse., Arch Oral Biol 1977;22(4):299-301
Green MC; Durham D; Mayer TC; Hoppe PC, Evidence from chimaeras for the pattern of proliferation of epidermis in the mouse., Genet Res 1977 Jun; 29(3):279-84
Crocker M; Cattanach BM, The genetics of Sleek: a possible regulatory mutation of the tabby-crinkled-downless syndrome., Genet Res 1979 Dec;34(3):231-8
Peters J; Andrews SJ; Beechey CV, Position of Hk-1 on Chromosome 10, Mouse News Lett 1980;63():17
Shawlot W; Siciliano MJ; Stallings RL; Overbeek PA, Insertional inactivation of the downless gene in a family of transgenic mice., Mol Biol Med 1989 Aug;6(4):299-307
Rao MS; Jaszczak E; Landis SC, Innervation of footpads of normal and mutant mice lacking sweat glands., J Comp Neurol 1994 Aug 22;346(4):613-25
Sundberg JP, The Downless (dl) and Sleek (Dl<slk>) Mutations, Chromosome 10, In: Handbook of Mouse Mutations with Skin and Hair Abnormalities: Animal Models and Biomedical Tools. Sundberg, JP (ed.), CRC Press, Boca Raton, FL, pp 241-246, 1994.
Majumder K; Shawlot W; Schuster G; Harrison W; Elder FF; Overbeek PA, YAC rescue of downless locus mutations in mice., Mamm Genome 1998 Nov; 9(11):863-8
Cook S, The Jackson Laboratory Mouse Mutant Resource 2000 Mutation Reports, MGI Direct Data Submission 2000;():
Huelsken J; Vogel R; Erdmann B; Cotsarelis G; Birchmeier W, beta-Catenin controls hair follicle morphogenesis and stem cell differentiation in the skin., Cell 2001 May 18;105(4):533-45
Schmidt-Ullrich R; Aebischer T; Hulsken J; Birchmeier W; Klemm U; Scheidereit C, Requirement of NF-kappaB/Rel for the development of hair follicles and other epidermal appendices., Development 2001 Oct;128(19):3843-53
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
Laurikkala J; Pispa J; Jung HS; Nieminen P; Mikkola M; Wang X; Saarialho-Kere U; Galceran J; Grosschedl R; Thesleff I, Regulation of hair follicle development by the TNF signal ectodysplasin and its receptor Edar., Development 2002 May;129(10):2541-53
Andl T; Reddy ST; Gaddapara T; Millar SE, WNT Signals Are Required for the Initiation of Hair Follicle Development., Dev Cell 2002 May;2(5):643-53
Jaskoll T; Zhou YM; Trump G; Melnick M, Ectodysplasin receptor-mediated signaling is essential for embryonic submandibular salivary gland development., Anat Rec 2003 Apr;271A(2):322-31
Sharov AA; Weiner L; Sharova TY; Siebenhaar F; Atoyan R; Reginato AM; McNamara CA; Funa K; Gilchrest BA; Brissette JL; Botchkarev VA, Noggin overexpression inhibits eyelid opening by altering epidermal apoptosis and differentiation., EMBO J 2003 Jun 16;22(12):2992-3003
Mustonen T; Pispa J; Mikkola ML; Pummila M; Kangas AT; Pakkasjarvi L; Jaatinen R; Thesleff I, Stimulation of ectodermal organ development by Ectodysplasin-A1., Dev Biol 2003 Jul 1;259(1):123- 36
Pispa J; Mikkola ML; Mustonen T; Thesleff I, Ectodysplasin, Edar and TNFRSF19 are expressed in complementary and overlapping patterns during mouse embryogenesis., Gene Expr Patterns 2003 Oct;3(5):675-9
Tucker AS; Headon DJ; Courtney JM; Overbeek P; Sharpe PT, The activation level of the TNF family receptor, Edar, determines cusp number and tooth number during tooth development., Dev Biol 2004 Apr 1;268(1):185-94
Aberg T; Wang XP; Kim JH; Yamashiro T; Bei M; Rice R; Ryoo HM; Thesleff I, Runx2 mediates FGF signaling from epithelium to mesenchyme during tooth morphogenesis., Dev Biol 2004 Jun 1;270(1):76-93
Wang XP; Suomalainen M; Jorgez CJ; Matzuk MM; Wankell M; Werner S; Thesleff I, Modulation of activin/bone morphogenetic protein signaling by follistatin is required for the morphogenesis of mouse molar teeth., Dev Dyn 2004 Sep; 231(1):98-108
Pispa J; Mustonen T; Mikkola ML; Kangas AT; Koppinen P; Lukinmaa PL; Jernvall J; Thesleff I, Tooth patterning and enamel formation can be manipulated by misexpression of TNF receptor Edar., Dev Dyn 2004 Oct; 231(2):432-40
