Rapid compensation for glycosylphosphatidylinositol anchor deficient keratinocytes after birth: visualization of glycosylphosphatidylinositol-anchored proteins in situ.
Pig-a, an X-linked gene, is a key component of glycosylphosphatidylinositol (GPI) anchor biosynthesis based on the fact that lack of this gene causes deficiencies of hundreds of GPI-anchored proteins. We previously demonstrated an essential role for the GPI-anchor in keratinocyte differentiation using male Pig-a knockout mice (K5-Cre:Pig-a flox). Here we analyzed keratinocytes of the female K5-Cre: Pig-a flox/+ mice with heterozygous knockout of Pig-a. These cells exhibited the mosaic pattern of GPI-anchor positive and negative expression typical of random inactivation of the X chromosome. The female K5-Cre:Pig-a flox/+ mice appeared slightly wrinkled with dry skin at birth and white scales starting from 4 d after birth without any histologic abnormality. This phenotype was temporary and milder than that seen in the male knockout mice. To characterize the fate of GPI-anchor-positive cells more clearly, we introduced a transgenic mouse line that expresses enhanced green fluorescent protein in GPI-anchored form into female K5-Cre:Pig-a flox/+ mice and monitored GPI-anchor-positive keratinocytes in situ. Within 36 h after birth, the upper layer of the GPI-anchor-negative zone in epidermis was replaced by the GPI-anchor-positive counterpart. This tissue replacement was accompanied by recovery in trans-epidermal water loss over a similar time course. These observations suggest that the GPI-anchoring is associated with the barrier function as well as with organized differentiation of the epidermis after birth.
Gao
Xing-Hua
XH
Department of Social and Environmental Medicine H3 and Department of Dermatology, Graduate School of Medicine, Osaka University, Japan.
Kondoh
Gen
G
Tarutani
Masahito
M
Hara
Mariko
M
Inoue
Shintaro
S
Nakanishi
Tomoko
T
Okabe
Masaru
M
Yamaguchi
Yuji
Y
Yoshikawa
Kunihiko
K
Itami
Satoshi
S
Takeda
Junji
J
D000818:Animals; D000831:Animals, Newborn; D003584:Cytological Techniques; D004303:Dosage Compensation, Genetic; D000078404:Epidermal Cells; D004817:Epidermis / Q000378:metabolism; D005260:Female; D017261:Glycosylphosphatidylinositols / Q000378:metabolism*; D049452:Green Fluorescent Proteins; D007202:Indicators and Reagents / Q000378:metabolism; D015603:Keratinocytes / Q000378:metabolism*; D008164:Luminescent Proteins / Q000235:genetics; D008297:Male; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D010641:Phenotype; D011247:Pregnancy; D013047:Specific Pathogen-Free Organisms
D017261:Glycosylphosphatidylinositols; D007202:Indicators and Reagents; D008164:Luminescent Proteins; D008565:Membrane Proteins; C080086:phosphatidylinositol glycan-class A protein; D049452:Green Fluorescent Proteins