Short tail with skin lesion phenotype occurs in transgenic mice with keratin-14 promoter-directed expression of mutant CXCR2.
CXCR2 plays an important role during cutaneous wound healing. Transgenic mice were generated using the keratin-14 promoter/enhancer to direct expression of wild-type human CXCR2 (K14hCXCR2 WT) or mutant CXCR2, in which the carboxyl-terminal domain (CTD) was truncated at Ser 331 and the dileucine AP-2 binding motif was mutated to alanine (K14hCXCR2 331T/LL/AA/IL/AA). Our results indicate that K14hCXCR2WT transgenic mice exhibited a normal phenotype, while K14hCXCR2 331T/LL/AA/IL/AA transgenic mice were born with tails of normal length, but three to eight days after birth their tails degenerated, leaving only a short tail stub. The tissue degeneration in the tail started between caudal somites with degeneration of bone and connective tissue distal to the constriction, which was replaced with stromal tissue heavily infiltrated with inflammatory cells. The tail lesion site revealed coagulation in enlarged vessels and marked edema that eventually led to loss of the distal tail. Moreover, 66% of the mice exhibited focal skin blemishes and inflammation that exhibited an increase in the number of sebaceous glands and blood vessels, enlargement of the hair follicles due to increased number of keratinocytes, reduction in the connective tissue content, and a thickening of the epidermis. Furthermore, immunohistochemical staining of the epidermis from tail tissue in the transgenic mice indicated a loss of the cell adhesion markers E-cadherin and desmoplakin. These data suggest that keratinocyte expression of a CTD mutant of CXCR2 has effects on homeostasis of the connective tissue in the tail, as well as the maintenance of the epidermis and its appendages.
Yu
Yingchun
Y
Department of Cancer Biology, Vanderbilt University School of Medicine, 23rd Ave. South at Pierce, Nashville, TN 37232, USA.
Su
Yingjun
Y
Opalenik
Susan R
SR
Sobolik-Delmaire
Tammy
T
Neel
Nicole F
NF
Zaja-Milatovic
Snjezana
S
Short
Sarah T
ST
Sai
Jiqing
J
Richmond
Ann
A
D000595:Amino Acid Sequence; D000818:Animals; D004742:Enhancer Elements, Genetic; D006801:Humans; D053547:Keratin-14 / Q000235:genetics*; D051379:Mice; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009154:Mutation; D011401:Promoter Regions, Genetic; D023063:Receptors, Interleukin-8B / Q000235:genetics*; D017384:Sequence Deletion; D012867:Skin / Q000473:pathology*; D013623:Tail / Q000002:abnormalities*
D053547:Keratin-14; D023063:Receptors, Interleukin-8B