Towards defining the pathogenesis of the hairless phenotype

A. A. Panteleyev, C. Van Der Veen, T. Rosenbach, S. Muller-Rover, V. E. Sokolov, Ralf Paus

Research output: Contribution to journalArticle

76 Citations (Scopus)

Abstract

Mutation of the hairless (hr) gene in mice causes severe abnormalities during the first hair follicle regression (catagen), resulting in complete baldness. Here, we further characterize how hairlessness develops in HRS/J hairless mouse skin (hr) by histology, histochemistry, immunohistology, and in situ hybridization. We show that, in hr skin, only two defined epithelial cell populations in the distal outer root sheath (ORS) retain their integrity, whereas the rest of the ORS disintegrates. The surviving distal ORS forms the characteristic utriculi, whereas the remnants of the bulge get isolated from other epithelial compartments, but retain the capacity to proliferate and to produce either columnar epithelial outgrowths or selected dermal cysts. Normal dermal papilla structures get lost during the development of hairlessness. Based on the patterns of keratin 17 mRNA and neural cell adhesion molecule antigen expression, and on the distribution of alkaline phosphatase activity, we propose that dermal cysts in hr skin arise from (i) the central ORS, (ii) bulge-derived cells, or (iii) the disintegrating proximal ORS under the influence of dermal papilla remnants. The hr mutation seems to disrupt the integrity of key functional tissue units in the hair follicle, possibly due to a dysregulation of normal, catagen- associated apoptosis and/or an impairment of cell adhesion, whereas the distal follicle epithelium (including its stem cell region) seems to be largely protected from this. Thus, hairless mice offer a unique model for dissecting the as yet obscure functional properties of the hr gene product in maintaining follicle integrity during normal catagen.

Original languageEnglish (US)
Pages (from-to)902-907
Number of pages6
JournalJournal of Investigative Dermatology
Volume110
Issue number6
DOIs
StatePublished - Jan 1 1998
Externally publishedYes

Fingerprint

Skin
Phenotype
Keratin-17
Genes
Neural Cell Adhesion Molecules
Histology
Hairless Mouse
Cell adhesion
Stem cells
Hair Follicle
Alkaline Phosphatase
Cysts
Tissue
Apoptosis
Antigens
Messenger RNA
Mutation
Alopecia
Cell Adhesion
In Situ Hybridization

Keywords

  • Apoptosis
  • Hair follicle
  • Keratin 17
  • NCAM
  • Stem cells
  • Trichoepithelioma

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Dermatology
  • Cell Biology

Cite this

Panteleyev, A. A., Van Der Veen, C., Rosenbach, T., Muller-Rover, S., Sokolov, V. E., & Paus, R. (1998). Towards defining the pathogenesis of the hairless phenotype. Journal of Investigative Dermatology, 110(6), 902-907. https://doi.org/10.1046/j.1523-1747.1998.00219.x

Towards defining the pathogenesis of the hairless phenotype. / Panteleyev, A. A.; Van Der Veen, C.; Rosenbach, T.; Muller-Rover, S.; Sokolov, V. E.; Paus, Ralf.

In: Journal of Investigative Dermatology, Vol. 110, No. 6, 01.01.1998, p. 902-907.

Research output: Contribution to journalArticle

Panteleyev, AA, Van Der Veen, C, Rosenbach, T, Muller-Rover, S, Sokolov, VE & Paus, R 1998, 'Towards defining the pathogenesis of the hairless phenotype', Journal of Investigative Dermatology, vol. 110, no. 6, pp. 902-907. https://doi.org/10.1046/j.1523-1747.1998.00219.x
Panteleyev AA, Van Der Veen C, Rosenbach T, Muller-Rover S, Sokolov VE, Paus R. Towards defining the pathogenesis of the hairless phenotype. Journal of Investigative Dermatology. 1998 Jan 1;110(6):902-907. https://doi.org/10.1046/j.1523-1747.1998.00219.x
Panteleyev, A. A. ; Van Der Veen, C. ; Rosenbach, T. ; Muller-Rover, S. ; Sokolov, V. E. ; Paus, Ralf. / Towards defining the pathogenesis of the hairless phenotype. In: Journal of Investigative Dermatology. 1998 ; Vol. 110, No. 6. pp. 902-907.
@article{151c72fae27c4c2eb393170f49f3e941,
title = "Towards defining the pathogenesis of the hairless phenotype",
abstract = "Mutation of the hairless (hr) gene in mice causes severe abnormalities during the first hair follicle regression (catagen), resulting in complete baldness. Here, we further characterize how hairlessness develops in HRS/J hairless mouse skin (hr) by histology, histochemistry, immunohistology, and in situ hybridization. We show that, in hr skin, only two defined epithelial cell populations in the distal outer root sheath (ORS) retain their integrity, whereas the rest of the ORS disintegrates. The surviving distal ORS forms the characteristic utriculi, whereas the remnants of the bulge get isolated from other epithelial compartments, but retain the capacity to proliferate and to produce either columnar epithelial outgrowths or selected dermal cysts. Normal dermal papilla structures get lost during the development of hairlessness. Based on the patterns of keratin 17 mRNA and neural cell adhesion molecule antigen expression, and on the distribution of alkaline phosphatase activity, we propose that dermal cysts in hr skin arise from (i) the central ORS, (ii) bulge-derived cells, or (iii) the disintegrating proximal ORS under the influence of dermal papilla remnants. The hr mutation seems to disrupt the integrity of key functional tissue units in the hair follicle, possibly due to a dysregulation of normal, catagen- associated apoptosis and/or an impairment of cell adhesion, whereas the distal follicle epithelium (including its stem cell region) seems to be largely protected from this. Thus, hairless mice offer a unique model for dissecting the as yet obscure functional properties of the hr gene product in maintaining follicle integrity during normal catagen.",
keywords = "Apoptosis, Hair follicle, Keratin 17, NCAM, Stem cells, Trichoepithelioma",
author = "Panteleyev, {A. A.} and {Van Der Veen}, C. and T. Rosenbach and S. Muller-Rover and Sokolov, {V. E.} and Ralf Paus",
year = "1998",
month = "1",
day = "1",
doi = "10.1046/j.1523-1747.1998.00219.x",
language = "English (US)",
volume = "110",
pages = "902--907",
journal = "Journal of Investigative Dermatology",
issn = "0022-202X",
publisher = "Nature Publishing Group",
number = "6",

}

TY - JOUR

T1 - Towards defining the pathogenesis of the hairless phenotype

AU - Panteleyev, A. A.

AU - Van Der Veen, C.

AU - Rosenbach, T.

AU - Muller-Rover, S.

AU - Sokolov, V. E.

AU - Paus, Ralf

PY - 1998/1/1

Y1 - 1998/1/1

N2 - Mutation of the hairless (hr) gene in mice causes severe abnormalities during the first hair follicle regression (catagen), resulting in complete baldness. Here, we further characterize how hairlessness develops in HRS/J hairless mouse skin (hr) by histology, histochemistry, immunohistology, and in situ hybridization. We show that, in hr skin, only two defined epithelial cell populations in the distal outer root sheath (ORS) retain their integrity, whereas the rest of the ORS disintegrates. The surviving distal ORS forms the characteristic utriculi, whereas the remnants of the bulge get isolated from other epithelial compartments, but retain the capacity to proliferate and to produce either columnar epithelial outgrowths or selected dermal cysts. Normal dermal papilla structures get lost during the development of hairlessness. Based on the patterns of keratin 17 mRNA and neural cell adhesion molecule antigen expression, and on the distribution of alkaline phosphatase activity, we propose that dermal cysts in hr skin arise from (i) the central ORS, (ii) bulge-derived cells, or (iii) the disintegrating proximal ORS under the influence of dermal papilla remnants. The hr mutation seems to disrupt the integrity of key functional tissue units in the hair follicle, possibly due to a dysregulation of normal, catagen- associated apoptosis and/or an impairment of cell adhesion, whereas the distal follicle epithelium (including its stem cell region) seems to be largely protected from this. Thus, hairless mice offer a unique model for dissecting the as yet obscure functional properties of the hr gene product in maintaining follicle integrity during normal catagen.

AB - Mutation of the hairless (hr) gene in mice causes severe abnormalities during the first hair follicle regression (catagen), resulting in complete baldness. Here, we further characterize how hairlessness develops in HRS/J hairless mouse skin (hr) by histology, histochemistry, immunohistology, and in situ hybridization. We show that, in hr skin, only two defined epithelial cell populations in the distal outer root sheath (ORS) retain their integrity, whereas the rest of the ORS disintegrates. The surviving distal ORS forms the characteristic utriculi, whereas the remnants of the bulge get isolated from other epithelial compartments, but retain the capacity to proliferate and to produce either columnar epithelial outgrowths or selected dermal cysts. Normal dermal papilla structures get lost during the development of hairlessness. Based on the patterns of keratin 17 mRNA and neural cell adhesion molecule antigen expression, and on the distribution of alkaline phosphatase activity, we propose that dermal cysts in hr skin arise from (i) the central ORS, (ii) bulge-derived cells, or (iii) the disintegrating proximal ORS under the influence of dermal papilla remnants. The hr mutation seems to disrupt the integrity of key functional tissue units in the hair follicle, possibly due to a dysregulation of normal, catagen- associated apoptosis and/or an impairment of cell adhesion, whereas the distal follicle epithelium (including its stem cell region) seems to be largely protected from this. Thus, hairless mice offer a unique model for dissecting the as yet obscure functional properties of the hr gene product in maintaining follicle integrity during normal catagen.

KW - Apoptosis

KW - Hair follicle

KW - Keratin 17

KW - NCAM

KW - Stem cells

KW - Trichoepithelioma

UR - http://www.scopus.com/inward/record.url?scp=0031808638&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0031808638&partnerID=8YFLogxK

U2 - 10.1046/j.1523-1747.1998.00219.x

DO - 10.1046/j.1523-1747.1998.00219.x

M3 - Article

C2 - 9620297

AN - SCOPUS:0031808638

VL - 110

SP - 902

EP - 907

JO - Journal of Investigative Dermatology

JF - Journal of Investigative Dermatology

SN - 0022-202X

IS - 6

ER -