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Directed expression of keratin 16 to the progenitor basal cells of transgenic mouse skin delays skin maturation.

Paladini RD, Coulombe PA - J. Cell Biol. (1998)

Bottom Line: Histologically, the epidermis is thickened because of hyperproliferation of transgenic basal cells, whereas the hair follicles are decreased in number, poorly developed, and hypoproliferative.Microscopically, the transgenic keratinocytes are hypertrophic and feature an altered keratin filament network and decreased cell-cell adhesion.We conclude that expression of K16 can significantly alter the response of skin keratinocytes to signaling cues, a distinctive property likely resulting from its unique COOH-terminal tail domain.

View Article: PubMed Central - PubMed

Affiliation: Department of Biological Chemistry, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.

ABSTRACT
We previously hypothesized that the type I keratin 16 (K16) plays a role in the process of keratinocyte activation that occurs in response to skin injury (Paladini, R.D., K. Takahashi, N.S. Bravo, and P.A. Coulombe. 1996. J. Cell Biol. 132:381-397). To further examine its properties in vivo, the human K16 cDNA was constitutively expressed in the progenitor basal layer of transgenic mouse skin using the K14 gene promoter. Mice that express approximately as much K16 protein as endogenous K14 display a dramatic postnatal phenotype that consists of skin that is hyperkeratotic, scaly, and essentially devoid of fur. Histologically, the epidermis is thickened because of hyperproliferation of transgenic basal cells, whereas the hair follicles are decreased in number, poorly developed, and hypoproliferative. Microscopically, the transgenic keratinocytes are hypertrophic and feature an altered keratin filament network and decreased cell-cell adhesion. The phenotype normalizes at approximately 5 wk after birth. In contrast, control mice expressing a K16-K14 chimeric protein to comparable levels are normal. The character and temporal evolution of the phenotype in the K16 transgenic mice are reminiscent of the activated EGF receptor- mediated signaling pathway in skin. In fact, tyrosine phosphorylation of the EGF receptor is increased in the newborn skin of K16 transgenic mice. We conclude that expression of K16 can significantly alter the response of skin keratinocytes to signaling cues, a distinctive property likely resulting from its unique COOH-terminal tail domain.

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Transmission electron microscopy of phenotypic transgenic mouse epidermis (No. 6 line). Ventral skin was isolated from 6-d-old  wild-type control and K16 homozygous littermates and processed for electron microscopy. (A and C) Low magnification of epidermis.  While all layers of the epidermis can be visualized in the control (A), only the basal and spinous layers can be seen in the phenotypic epidermis (C), underscoring the dramatic difference in thickness between the two. (B and D) Basal cells shown at higher magnification. (B)  Control mouse epidermis. (D) Phenotypic K16 transgenic mouse epidermis shown at the same magnification. Note the elongated shape  of the basal cells, the bundling of keratin filaments (kf), cytoplasmic areas devoid of keratin filaments (large asterisks), and the numerous gaps between cells (small asterisks). The inset shows electron dense inclusions in mitochondria (short arrows) near the nucleus of a  suprabasal cell. Large arrowheads, the basal lamina. Small arrowheads, desmosomes. ba, basal layer; sp, stratum spinosum; sg, stratum  granulosum; sc, stratum corneum; Nu, nucleus; m, mitochondria; kf, keratin filaments. Bars: (A and C) 10 μm; (B and D) 2 μm.
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Figure 7: Transmission electron microscopy of phenotypic transgenic mouse epidermis (No. 6 line). Ventral skin was isolated from 6-d-old wild-type control and K16 homozygous littermates and processed for electron microscopy. (A and C) Low magnification of epidermis. While all layers of the epidermis can be visualized in the control (A), only the basal and spinous layers can be seen in the phenotypic epidermis (C), underscoring the dramatic difference in thickness between the two. (B and D) Basal cells shown at higher magnification. (B) Control mouse epidermis. (D) Phenotypic K16 transgenic mouse epidermis shown at the same magnification. Note the elongated shape of the basal cells, the bundling of keratin filaments (kf), cytoplasmic areas devoid of keratin filaments (large asterisks), and the numerous gaps between cells (small asterisks). The inset shows electron dense inclusions in mitochondria (short arrows) near the nucleus of a suprabasal cell. Large arrowheads, the basal lamina. Small arrowheads, desmosomes. ba, basal layer; sp, stratum spinosum; sg, stratum granulosum; sc, stratum corneum; Nu, nucleus; m, mitochondria; kf, keratin filaments. Bars: (A and C) 10 μm; (B and D) 2 μm.

Mentions: To finely characterize the cytoarchitectural changes in the keratinocytes of the phenotypic epidermis, ventral skin from 6-d-old littermates was examined using transmission electron microscopy. The control epidermis appears normal at low magnification (Fig. 7 A) All of the layers of the epidermis, from the basal cells to the stratum corneum, are clearly observed along with the distinctive features of each layer.


Directed expression of keratin 16 to the progenitor basal cells of transgenic mouse skin delays skin maturation.

Paladini RD, Coulombe PA - J. Cell Biol. (1998)

Transmission electron microscopy of phenotypic transgenic mouse epidermis (No. 6 line). Ventral skin was isolated from 6-d-old  wild-type control and K16 homozygous littermates and processed for electron microscopy. (A and C) Low magnification of epidermis.  While all layers of the epidermis can be visualized in the control (A), only the basal and spinous layers can be seen in the phenotypic epidermis (C), underscoring the dramatic difference in thickness between the two. (B and D) Basal cells shown at higher magnification. (B)  Control mouse epidermis. (D) Phenotypic K16 transgenic mouse epidermis shown at the same magnification. Note the elongated shape  of the basal cells, the bundling of keratin filaments (kf), cytoplasmic areas devoid of keratin filaments (large asterisks), and the numerous gaps between cells (small asterisks). The inset shows electron dense inclusions in mitochondria (short arrows) near the nucleus of a  suprabasal cell. Large arrowheads, the basal lamina. Small arrowheads, desmosomes. ba, basal layer; sp, stratum spinosum; sg, stratum  granulosum; sc, stratum corneum; Nu, nucleus; m, mitochondria; kf, keratin filaments. Bars: (A and C) 10 μm; (B and D) 2 μm.
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Figure 7: Transmission electron microscopy of phenotypic transgenic mouse epidermis (No. 6 line). Ventral skin was isolated from 6-d-old wild-type control and K16 homozygous littermates and processed for electron microscopy. (A and C) Low magnification of epidermis. While all layers of the epidermis can be visualized in the control (A), only the basal and spinous layers can be seen in the phenotypic epidermis (C), underscoring the dramatic difference in thickness between the two. (B and D) Basal cells shown at higher magnification. (B) Control mouse epidermis. (D) Phenotypic K16 transgenic mouse epidermis shown at the same magnification. Note the elongated shape of the basal cells, the bundling of keratin filaments (kf), cytoplasmic areas devoid of keratin filaments (large asterisks), and the numerous gaps between cells (small asterisks). The inset shows electron dense inclusions in mitochondria (short arrows) near the nucleus of a suprabasal cell. Large arrowheads, the basal lamina. Small arrowheads, desmosomes. ba, basal layer; sp, stratum spinosum; sg, stratum granulosum; sc, stratum corneum; Nu, nucleus; m, mitochondria; kf, keratin filaments. Bars: (A and C) 10 μm; (B and D) 2 μm.
Mentions: To finely characterize the cytoarchitectural changes in the keratinocytes of the phenotypic epidermis, ventral skin from 6-d-old littermates was examined using transmission electron microscopy. The control epidermis appears normal at low magnification (Fig. 7 A) All of the layers of the epidermis, from the basal cells to the stratum corneum, are clearly observed along with the distinctive features of each layer.

Bottom Line: Histologically, the epidermis is thickened because of hyperproliferation of transgenic basal cells, whereas the hair follicles are decreased in number, poorly developed, and hypoproliferative.Microscopically, the transgenic keratinocytes are hypertrophic and feature an altered keratin filament network and decreased cell-cell adhesion.We conclude that expression of K16 can significantly alter the response of skin keratinocytes to signaling cues, a distinctive property likely resulting from its unique COOH-terminal tail domain.

View Article: PubMed Central - PubMed

Affiliation: Department of Biological Chemistry, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.

ABSTRACT
We previously hypothesized that the type I keratin 16 (K16) plays a role in the process of keratinocyte activation that occurs in response to skin injury (Paladini, R.D., K. Takahashi, N.S. Bravo, and P.A. Coulombe. 1996. J. Cell Biol. 132:381-397). To further examine its properties in vivo, the human K16 cDNA was constitutively expressed in the progenitor basal layer of transgenic mouse skin using the K14 gene promoter. Mice that express approximately as much K16 protein as endogenous K14 display a dramatic postnatal phenotype that consists of skin that is hyperkeratotic, scaly, and essentially devoid of fur. Histologically, the epidermis is thickened because of hyperproliferation of transgenic basal cells, whereas the hair follicles are decreased in number, poorly developed, and hypoproliferative. Microscopically, the transgenic keratinocytes are hypertrophic and feature an altered keratin filament network and decreased cell-cell adhesion. The phenotype normalizes at approximately 5 wk after birth. In contrast, control mice expressing a K16-K14 chimeric protein to comparable levels are normal. The character and temporal evolution of the phenotype in the K16 transgenic mice are reminiscent of the activated EGF receptor- mediated signaling pathway in skin. In fact, tyrosine phosphorylation of the EGF receptor is increased in the newborn skin of K16 transgenic mice. We conclude that expression of K16 can significantly alter the response of skin keratinocytes to signaling cues, a distinctive property likely resulting from its unique COOH-terminal tail domain.

Show MeSH
Related in: MedlinePlus