Stem cell factor rescues tyrosinase expression and pigmentation in discreet anatomic locations in albino mice.
The K14-SCF transgenic murine model of variant pigmentation is based on epidermal expression of stem cell factor (SCF) on the C57BL/6J background. In this system, constitutive expression of SCF by epidermal keratinocytes results in retention of melanocytes in the interfollicular basal layer and pigmentation of the epidermis itself. Here, we extend this animal model by developing a compound mutant transgenic amelanotic animal defective at both the melanocortin 1 receptor (Mc1r) and tyrosinase (Tyr) loci. In the presence of K14-Scf, tyrosinase-mutant animals (previously thought incapable of synthesizing melanin) exhibited progressive robust epidermal pigmentation with age in the ears and tails. Furthermore, K14-SCF Tyr(c2j/c2j) animals demonstrated tyrosinase expression and enzymatic activity, suggesting that the c2j Tyr defect can be rescued in part by SCF in the ears and tail. Lastly, UV sensitivity of K14-Scf congenic animals depended mainly on the amount of eumelanin present in the skin. These findings suggest that c-kit signaling can overcome the c2j Tyr mutation in the ears and tails of aging animals and that UV resistance depends on accumulation of epidermal eumelanin.
Vanover
Jillian C
JC
Department of Pediatrics, University of Kentucky College of Medicine, the Markey Cancer Center, the Graduate Center for Toxicology, Lexington, KY, USA.
Spry
Malinda L
ML
Hamilton
Laura
L
Wakamatsu
Kazumasa
K
Ito
Shosuke
S
D'Orazio
John A
JA
D000818:Animals; D000078404:Epidermal Cells; D004817:Epidermis / Q000378:metabolism / Q000528:radiation effects; D006200:Hair Color / Q000502:physiology; D006801:Humans; D008544:Melanocytes / Q000166:cytology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D014442:Monophenol Monooxygenase / Q000235:genetics / Q000378:metabolism*; D010641:Phenotype; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D012880:Skin Pigmentation / Q000502:physiology*; D019089:Stem Cell Factor / Q000235:genetics / Q000378:metabolism*; D014466:Ultraviolet Rays
D019089:Stem Cell Factor; D014442:Monophenol Monooxygenase; D019009:Proto-Oncogene Proteins c-kit
Pigment Cell Res. 2002 Jun;15(3):174-83
12028581
Photochem Photobiol. 2003 Jan;77(1):41-5
12856881
Cell. 1993 Mar 26;72(6):827-34
8458079
J Am Acad Dermatol. 1981 Oct;5(4):439-43
7287960
Photochem Photobiol. 2005 Jan-Feb;81(1):145-8
15458368
Br J Dermatol. 1983 Jan;108(1):1-9
6821636
Nature. 2006 Sep 21;443(7109):340-4
16988713
J Neurochem. 2003 Aug;86(4):1015-23
12887698
Pigment Cell Res. 2000;13 Suppl 8:140-4
11041372
J Invest Dermatol. 1993 Feb;100(2 Suppl):166S-171S
8433004
J Exp Med. 1998 May 18;187(10):1565-73
9584135
Pigment Cell Res. 2002 Aug;15(4):290-7
12100495
Clin Exp Pharmacol Physiol. 2007 May-Jun;34(5-6):499-507
17439422
Dev Biol. 1997 Dec 1;192(1):99-107
9405100
Am J Dermatopathol. 1984 Summer;6 Suppl:143-5
6084955
Proc Natl Acad Sci U S A. 2004 Oct 19;101(42):15076-81
15477596
Eur J Morphol. 2001 Jul;39(3):169-91
11910536
FASEB J. 2006 Jul;20(9):1561-3
16723376
Genomics. 1996 Oct 15;37(2):245-8
8921397
J Invest Dermatol. 1979 Oct;73(4):306-9
479635
Proc Natl Acad Sci U S A. 1995 Feb 28;92(5):1789-93
7878059