|
Originally published In Press as doi:10.1074/jbc.M205143200 on July 15, 2002
J. Biol. Chem., Vol. 277, Issue 38, 35371-35377, September 20, 2002
Severe Abnormalities in the Oral Mucosa Induced by Suprabasal
Expression of Epidermal Keratin K10 in Transgenic Mice*
Mirentxu
Santos ,
Ana
Bravo§,
Ceferino
López§,
Jesús M.
Paramio ¶, and
José L.
Jorcano
From the Project on Cell and Molecular Biology and
Gene Therapy, CIEMAT Av. Complutense 22, E-28040 Madrid, Spain and the
§ Department of Animal Pathology, Veterinary School,
University of Santiago de Compostela, 27002 Lugo, Spain
Previous studies have demonstrated that keratin
K10 plays an important role in mediating cell signaling processes,
since the ectopic expression of this keratin induces cell cycle arrest
in proliferating cells in vitro and in vivo.
However, apart from its well known function of providing epithelial
cells with resilience to mechanical trauma, little is known about its
possible roles in nondividing cells. To investigate what these might
be, transgenic mice were generated in which the expression of K10 was
driven by bovine K6 gene control elements (bK6 hK10). The
transgenic mice displayed severe abnormalities in the tongue and palate
but not in other K6-expressing cells such as those of the esophagus, nails, and hair follicles. The lesions in the tongue and palate included the cytolysis of epithelial suprabasal cells associated with
an acute inflammatory response and lymphocyte infiltration. The
alterations in the oral mucosa caused the death of transgenic pups soon
after birth, probably because suckling was impaired. These anomalies,
together with others found in the teeth, are reminiscent of the lesions
observed in some patients with pachyonychia congenita, an inherited
epithelial fragility associated with mutations in keratins K6 and K16.
Although no epithelial fragility was observed in the bK6 hK10 oral
epithelia of the experimental mice, necrotic processes were
seen. Collectively, these data show that the carefully regulated
tissue- and differentiation-specific patterns displayed by the keratin
genes have dramatic consequences on the biological behavior of
epithelial cells and that changes in the specific composition of the
keratin intermediate filament cytoskeleton can affect their physiology,
in particular those of the oral mucosa.
*
This work was supported in part by Spanish MCYT Grant
PB94-1230 and CAM Grant 08.1/0054/2001.1.The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
¶
To whom correspondence should be addressed. Tel.:
34-91-3466438; Fax: 34-91346484; E-mail:
jesusm.paramio@ciemat.es.
Copyright © 2002 by The American Society for Biochemistry and Molecular Biology, Inc.

CiteULike Complore Connotea Del.icio.us Digg Reddit Technorati What's this?
This article has been cited by other articles:

|
 |

|
 |
 
G. Fitsialos, A.-A. Chassot, L. Turchi, M. A. Dayem, K. LeBrigand, C. Moreilhon, G. Meneguzzi, R. Busca, B. Mari, P. Barbry, et al.
Transcriptional Signature of Epidermal Keratinocytes Subjected to in Vitro Scratch Wounding Reveals Selective Roles for ERK1/2, p38, and Phosphatidylinositol 3-Kinase Signaling Pathways
J. Biol. Chem.,
May 18, 2007;
282(20):
15090 - 15102.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
B. K. Bloor, N. Tidman, I. M. Leigh, E. Odell, B. Dogan, U. Wollina, L. Ghali, and A. Waseem
Expression of Keratin K2e in Cutaneous and Oral Lesions: Association with Keratinocyte Activation, Proliferation, and Keratinization
Am. J. Pathol.,
March 1, 2003;
162(3):
963 - 975.
[Abstract]
[Full Text]
[PDF]
|
 |
|
Copyright © 2002 by the American Society for Biochemistry and Molecular Biology.
|
Advertisement
Advertisement
|