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The functional diversity of epidermal keratins revealed by the partial rescue of the keratin 14 phenotype by keratin 16.

Paladini RD, Coulombe PA - J. Cell Biol. (1999)

Bottom Line: Degenstein, E.Fuchs. 1995.Despite their high sequence similarity, K16 and K14 are not functionally equivalent in the epidermis and other stratified epithelia and it is primarily the carboxy-terminal approximately 105 amino acids of K16 that define these differences.

View Article: PubMed Central - PubMed

Affiliation: Departments of Biological Chemistry and Dermatology, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.

ABSTRACT
The type I epidermal keratins K14 and K16 are remarkably similar at the primary sequence level. While a structural function has been clearly defined for K14, we have proposed that a function of K16 may be to play a role in the process of keratinocyte activation that occurs after acute injury to stratified epithelia. To compare directly the functions of the two keratins we have targeted the expression of the human K16 cDNA to the progenitor basal layer of the epidermis of K14 mice. Mice for K14 blister extensively and die approximately 2 d after birth (Lloyd, C., Q.C. Yu, J. Cheng, K. Turksen, L. Degenstein, E. Hutton, and E. Fuchs. 1995. J. Cell Biol. 129:1329-1344). The skin of mice expressing K16 in the absence of K14 developed normally without evidence of blistering. However, as the mice aged they featured extensive alopecia, chronic epidermal ulcers in areas of frequent physical contact, and alterations in other stratified epithelia. Mice expressing a control K16-C14 cDNA also rescue the blistering phenotype of the K14 mice with only a small percentage exhibiting minor alopecia. While K16 is capable of rescuing the blistering, phenotypic complementation in the resulting skin is incomplete due to the multiple age dependent anomalies. Despite their high sequence similarity, K16 and K14 are not functionally equivalent in the epidermis and other stratified epithelia and it is primarily the carboxy-terminal approximately 105 amino acids of K16 that define these differences.

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Hair regrowth in the K16 replacement mice. A K16 replacement mouse that featured dorsal alopecia was treated with a depilatory agent to determine if hair regrowth could occur (A). Immediately after depilation, the hairless area had a darker color than the surrounding skin (B). 5 d after treatment (C) hair regrowth in the previously hairless area was apparent while growth in the previously hairy areas had not yet occurred. 2 wk after treatment (D) hair regrowth in both areas is obvious. Arrowhead, indicates the boundary between the hairless and hairy skin areas.
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Figure 10: Hair regrowth in the K16 replacement mice. A K16 replacement mouse that featured dorsal alopecia was treated with a depilatory agent to determine if hair regrowth could occur (A). Immediately after depilation, the hairless area had a darker color than the surrounding skin (B). 5 d after treatment (C) hair regrowth in the previously hairless area was apparent while growth in the previously hairy areas had not yet occurred. 2 wk after treatment (D) hair regrowth in both areas is obvious. Arrowhead, indicates the boundary between the hairless and hairy skin areas.

Mentions: The electron microscopy data from hairless K16 replacement skin suggested that there were major morphological alterations in the outer root sheath of the hair follicle, the hair shaft, and in the correct cycling of the follicles. Hairless and hairy regions of K16 replacement skin were treated with a depilatory agent to remove existing hairs and to stimulate the anagen phase of the hair cycle (Fig. 10 A). Immediately after treatment the regions of skin that were previously hairless had a much darker color compared with the areas that were hairy (Fig. 10 B). As early as 2 d after treatment there were signs of hair regrowth in the region that was previously devoid of hair (data not shown). Five days after treatment with the depilatory agent hair regrowth was obvious in the previously hairless region (Fig. 10 C) while hair regrowth had not occurred in the previously hairy regions. After 2 wk (Fig. 10 D) the regrown hairs were quite long and hair growth in some of the previously hairy regions had also occurred. Hair regrowth in these regions was slower and more sporadic as some of these areas remained hairless for many weeks after the treatment (data not shown). These results clearly indicate that hair cycle progression and hair growth is aberrant in the K16 replacement mice.


The functional diversity of epidermal keratins revealed by the partial rescue of the keratin 14 phenotype by keratin 16.

Paladini RD, Coulombe PA - J. Cell Biol. (1999)

Hair regrowth in the K16 replacement mice. A K16 replacement mouse that featured dorsal alopecia was treated with a depilatory agent to determine if hair regrowth could occur (A). Immediately after depilation, the hairless area had a darker color than the surrounding skin (B). 5 d after treatment (C) hair regrowth in the previously hairless area was apparent while growth in the previously hairy areas had not yet occurred. 2 wk after treatment (D) hair regrowth in both areas is obvious. Arrowhead, indicates the boundary between the hairless and hairy skin areas.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2169494&req=5

Figure 10: Hair regrowth in the K16 replacement mice. A K16 replacement mouse that featured dorsal alopecia was treated with a depilatory agent to determine if hair regrowth could occur (A). Immediately after depilation, the hairless area had a darker color than the surrounding skin (B). 5 d after treatment (C) hair regrowth in the previously hairless area was apparent while growth in the previously hairy areas had not yet occurred. 2 wk after treatment (D) hair regrowth in both areas is obvious. Arrowhead, indicates the boundary between the hairless and hairy skin areas.
Mentions: The electron microscopy data from hairless K16 replacement skin suggested that there were major morphological alterations in the outer root sheath of the hair follicle, the hair shaft, and in the correct cycling of the follicles. Hairless and hairy regions of K16 replacement skin were treated with a depilatory agent to remove existing hairs and to stimulate the anagen phase of the hair cycle (Fig. 10 A). Immediately after treatment the regions of skin that were previously hairless had a much darker color compared with the areas that were hairy (Fig. 10 B). As early as 2 d after treatment there were signs of hair regrowth in the region that was previously devoid of hair (data not shown). Five days after treatment with the depilatory agent hair regrowth was obvious in the previously hairless region (Fig. 10 C) while hair regrowth had not occurred in the previously hairy regions. After 2 wk (Fig. 10 D) the regrown hairs were quite long and hair growth in some of the previously hairy regions had also occurred. Hair regrowth in these regions was slower and more sporadic as some of these areas remained hairless for many weeks after the treatment (data not shown). These results clearly indicate that hair cycle progression and hair growth is aberrant in the K16 replacement mice.

Bottom Line: Degenstein, E.Fuchs. 1995.Despite their high sequence similarity, K16 and K14 are not functionally equivalent in the epidermis and other stratified epithelia and it is primarily the carboxy-terminal approximately 105 amino acids of K16 that define these differences.

View Article: PubMed Central - PubMed

Affiliation: Departments of Biological Chemistry and Dermatology, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.

ABSTRACT
The type I epidermal keratins K14 and K16 are remarkably similar at the primary sequence level. While a structural function has been clearly defined for K14, we have proposed that a function of K16 may be to play a role in the process of keratinocyte activation that occurs after acute injury to stratified epithelia. To compare directly the functions of the two keratins we have targeted the expression of the human K16 cDNA to the progenitor basal layer of the epidermis of K14 mice. Mice for K14 blister extensively and die approximately 2 d after birth (Lloyd, C., Q.C. Yu, J. Cheng, K. Turksen, L. Degenstein, E. Hutton, and E. Fuchs. 1995. J. Cell Biol. 129:1329-1344). The skin of mice expressing K16 in the absence of K14 developed normally without evidence of blistering. However, as the mice aged they featured extensive alopecia, chronic epidermal ulcers in areas of frequent physical contact, and alterations in other stratified epithelia. Mice expressing a control K16-C14 cDNA also rescue the blistering phenotype of the K14 mice with only a small percentage exhibiting minor alopecia. While K16 is capable of rescuing the blistering, phenotypic complementation in the resulting skin is incomplete due to the multiple age dependent anomalies. Despite their high sequence similarity, K16 and K14 are not functionally equivalent in the epidermis and other stratified epithelia and it is primarily the carboxy-terminal approximately 105 amino acids of K16 that define these differences.

Show MeSH
Related in: MedlinePlus