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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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Light microscopy of hair from control and transgenic  mice (No. 10 line). Dorsal hairs from a 41-d-old wild-type and homozygous transgenic litter mate were placed on slides, coverslipped, and examined using light microscopy. Control hairs (B)  are long and straight whereas the hairs from the homozygous littermate (A) are shorter and feature distal ends that are curved  and sickle shaped. Bar, 100 μm.
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Figure 4: Light microscopy of hair from control and transgenic mice (No. 10 line). Dorsal hairs from a 41-d-old wild-type and homozygous transgenic litter mate were placed on slides, coverslipped, and examined using light microscopy. Control hairs (B) are long and straight whereas the hairs from the homozygous littermate (A) are shorter and feature distal ends that are curved and sickle shaped. Bar, 100 μm.

Mentions: Dorsal hairs from 41-d-old wild-type, heterozygous, and homozygous littermates were obtained and examined using light microscopy. Hairs from the homozygous mouse were shorter and the distal ends were often curved and shaped like a sickle (Fig. 4 A). Approximately 80% of the hairs from the homozygous mouse featured this abnormal shape. This same morphology was present in dorsal hair examined from older (6 mo) homozygous mice although the frequency was slightly lower (∼60%). Hair from wild-type (Fig. 4 B), and heterozygous littermates (data not shown) were long and featured straight distal ends. Essentially all of the hairs examined (98%) featured this morphology. The morphology of the phenotypic hairs were very similar to those obtained by Moore et al. (61) in their study in which they treated newborn mice with subcutaneous injections of EGF. Hairs from the first coat of these mice were reduced in diameter, shorter, and featured curvature of the distal ends.


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)

Light microscopy of hair from control and transgenic  mice (No. 10 line). Dorsal hairs from a 41-d-old wild-type and homozygous transgenic litter mate were placed on slides, coverslipped, and examined using light microscopy. Control hairs (B)  are long and straight whereas the hairs from the homozygous littermate (A) are shorter and feature distal ends that are curved  and sickle shaped. Bar, 100 μm.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2132878&req=5

Figure 4: Light microscopy of hair from control and transgenic mice (No. 10 line). Dorsal hairs from a 41-d-old wild-type and homozygous transgenic litter mate were placed on slides, coverslipped, and examined using light microscopy. Control hairs (B) are long and straight whereas the hairs from the homozygous littermate (A) are shorter and feature distal ends that are curved and sickle shaped. Bar, 100 μm.
Mentions: Dorsal hairs from 41-d-old wild-type, heterozygous, and homozygous littermates were obtained and examined using light microscopy. Hairs from the homozygous mouse were shorter and the distal ends were often curved and shaped like a sickle (Fig. 4 A). Approximately 80% of the hairs from the homozygous mouse featured this abnormal shape. This same morphology was present in dorsal hair examined from older (6 mo) homozygous mice although the frequency was slightly lower (∼60%). Hair from wild-type (Fig. 4 B), and heterozygous littermates (data not shown) were long and featured straight distal ends. Essentially all of the hairs examined (98%) featured this morphology. The morphology of the phenotypic hairs were very similar to those obtained by Moore et al. (61) in their study in which they treated newborn mice with subcutaneous injections of EGF. Hairs from the first coat of these mice were reduced in diameter, shorter, and featured curvature of the distal ends.

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