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Matriptase/MT-SP1 is required for postnatal survival, epidermal barrier function, hair follicle development, and thymic homeostasis

Oncogene volume 21, pages 3765–3779 (2002)Cite this article

Abstract

Matriptase/MT-SP1 is a novel tumor-associated type II transmembrane serine protease that is highly expressed in the epidermis, thymic stroma, and other epithelia. A null mutation was introduced into the Matriptase/MT-SP1 gene of mice to determine the role of Matriptase/MT-SP1 in epidermal development and neoplasia. Matriptase/MT-SP1-deficient mice developed to term but uniformly died within 48 h of birth. All epidermal surfaces of newborn mice were grossly abnormal with a dry, red, shiny, and wrinkled appearance. Matriptase/MT-SP1-deficiency caused striking malformations of the stratum corneum, characterized by dysmorphic and pleomorphic corneocytes and the absence of vesicular bodies in transitional layer cells. This aberrant skin development seriously compromised both inward and outward epidermal barrier function, leading to the rapid and fatal dehydration of Matriptase/MT-SP1-deficient pups. Loss of Matriptase/MT-SP1 also seriously affected hair follicle development resulting in generalized follicular hypoplasia, absence of erupted vibrissae, lack of vibrissal hair canal formation, ingrown vibrissae, and wholesale abortion of vibrissal follicles. Furthermore, Matriptase/MT-SP1-deficiency resulted in dramatically increased thymocyte apoptosis, and depletion of thymocytes. This study demonstrates that Matriptase/MT-SP1 has pleiotropic functions in the development of the epidermis, hair follicles, and cellular immune system.

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References

  • Andreasen PA, Christensen TH, Huang JY, Nielsen LS, Wilson EL, Dano K . 1986 Mol. Cell. Endocrinol. 45: 137–147

  • Andreasen PA, Egelund R, Petersen HH . 2000 Cell. Mol. Life Sci. 57: 25–40

  • Appel LF, Prout M, Abu-Shumays R, Hammonds A, Garbe JC, Fristrom D, Fristrom J . 1993 Proc. Natl. Acad. Sci. USA 90: 4937–4941

  • Benaud C, Dickson RB, Lin CY . 2001 Eur. J. Biochem. 268: 1439–1447

  • Blobel CP . 2000 Curr. Opin. Cell. Biol. 12: 606–612

  • Carmeliet P, Schoonjans L, Kieckens L, Ream B, Degen J, Bronson R, De Vos R, van den Oord JJ, Collen D, Mulligan RC . 1994 Nature 368: 419–424

  • Chen W, Jin W, Tian H, Sicurello P, Frank M, Orenstein JM, Wahl SM . 2001 J. Exp. Med. 194: 439–453

  • Damiano BP, Cheung WM, Santulli RJ, Fung-Leung WP, Ngo K, Ye RD, Darrow AL, Derian CK, de Garavilla L, Andrade-Gordon P . 1999 J. Pharmacol. Exp. Ther. 288: 671–678

  • Davidson P, Hardy M . 1952 J. Anat. 86: 342–356

  • Davisson MT, Cook SA, Johnson KR, Eicher EM . 1994 J. Hered. 85: 134–136

  • De Laurenzi V, Rogers GR, Hamrock DJ Marekov LN, Steinert PM, Compton JG, Markova N, Rizzo WB . 1996 Nat. Genet. 12: 52–57

  • Elias PM, Matsuyoshi N, Wu H, Lin C, Wang ZH, Brown BE, Stanley JR . 2001 J. Cell. Biol. 153: 243–249

  • Esler WP, Wolfe MS . 2001 Science 293: 1449–1454

  • Flanagan SP . 1966 Genet. Res. 8: 295–309

  • Hooper JD, Clements JA, Quigley JP, Antalis TM . 2001 J. Biol. Chem. 276: 857–860

  • Huber M, Rettler I, Bernasconi K, Frenk E, Lavrijsen SP, Ponec M, Bon A, Lautenschlager S, Schorderet DF, Hohl D . 1995 Science 267: 525–528

  • Jensen PJ, Lavker RM . 1999 J. Invest. Dermatol. 112: 240–244

  • Jindo T, Tsuboi R, Takamori K, Ogawa H . 1998 J. Invest. Dermatol. 110: 338–342

  • Kaufmann MH, Bart S . 1999 The anatomical basis of mouse development Revised edition San Diego, CA: Academic Press

    Google Scholar 

  • Kim MG, Chen C, Lyu MS, Cho EG, Park D, Kozak C, Schwartz RH . 1999 Immunogenetics 49: 420–428

  • Koch PJ, de Viragh PA, Schrarer E, Bundman D, Longley MA, Bickenbach J, Kawachi Y, Suga Y, Zhou Z, Huber M, Hohl D, Kartasova T, Jarnik M, Steven AC, Roop DR . 2000 J. Cell. Biol. 151: 389–400

  • Kubilus J, Tarascio AJ, Baden HP . 1979 Am. J. Hum. Genet. 31: 50–53

  • Lee SL, Dickson RB, Lin CY . 2000 J. Biol. Chem. 275: 36720–36725

  • Lee YR, Yamazaki M, Mitsui S, Tsuboi R, Ogawa H . 2001 J. Dermatol. Sci. 25: 156–163

  • Lin CY, Anders J, Johnson M, Dickson RB . 1999 J. Biol. Chem. 274: 18237–18242

  • Lindner G, Menrad A, Gherardi E, Merlino G, Welker P, Handjiski B, Roloff B, Paus R . 2000a FASEB J. 14: 319–332

  • Lindner JR, Kahn ML, Coughlin SR, Sambrano GR, Schauble E, Berstein D, Foy D, Hafezi-Moghadam A, Ley K . 2000b J. Immunol. 165: 6504–6510

  • Luttun A, Dewerchin M, Collen D, Carmeliet P . 2000 Curr. Atheroscler. Rep. 2: 407–416

  • Magerl M, Tobin DJ, Muller-Rover S, Hagen E, Lindner G, McKay IA, Paus R . 2001 J. Invest. Dermatol. 116: 947–955

  • Magin TM, McWhir J, Melton DW . 1992 Nucleic. Acids Res. 20: 3795–3796

  • Manley NR . 2000 Semin. Immunol. 12: 421–428

  • Mann NS, Mann SK . 1994 Proc. Soc. Exp. Bio. Med. 206: 114–118

  • Matrisian LM . 1999 Curr. Biol. 9: R776–R778

  • Matsuki M, Yamashita F, Ishida-Yamamoto A, Yamada K, Kinoshita C, Fushiki S, Ueda E, Morishima Y, Tabata K, Yasuno H, Hashida M, Iizuka H, Ikawa M, Okabe M, Kondoh G, Kinoshita T, Takeda J, Yamanishi K . 1998 Proc. Natl. Acad. Sci. USA 95: 1044–1049

  • McCawley LJ, O'Brien P, Hudson LG . 1998 J. Cell Physiol. 176: 255–265

  • Nakagawa T, Roth W, Wong P, Nelson A, Farr A, Deussing J, Villadangos JA, Ploegh H, Peters C, Rudensky AY . 1998 Science 280: 450–453

  • Nemes Z, Steinert PM . 1999 Exp. Mol. Med. 31: 5–19

  • Oberst M, Anders J, Xie B, Singh B, Ossandon M, Johnson M, Dickson RB, Lin CY . 2001 Am. J. Pathol. 158: 1301–1311

  • Presland RB, Dale BA . 2000 Crit. Rev. Oral. Biol. Med. 11: 383–408

  • Reske-Kunz AB, Scheid MP, Boyse EA . 1979 J. Exp. Med. 149: 228–233

  • Roop D . 1995 Science 267: 474–475

  • Russell LJ, DiGiovanna JJ, Rogers GR, Steinert PM, Hashem N, Compton JG, Bale SJ . 1995 Nat. Genet. 9: 279–283

  • Scott HS, Kudoh J, Wattenhofer M, Shibuya K, Berry A, Chrast R, Guipponi M, Wang J, Kawasaki K, Asakawa S, Minoshima S, Younus F, Mehdi SQ, Radhakrishna U, Papasavvas MP, Gehrig C, Rossier C, Korostishevsky M, Gal A, Shimizu N, Bonne-Tamir B, Antonarakis SE . 2001 Nat. Genet. 27: 59–63

  • Sebzda E, Mariathasan S, Ohteki T, Jones R, Bachmann MF, Ohashi PS . 1999 Annu. Rev. Immunol. 17: 829–874

  • Shapiro LJ, Weiss R, Buxman MM, Vidgoff J, Dimond RL, Roller JA, Wells RS . 1978 Lancet 2: 756–757

  • Shultz LD . 1988 Curr. Top. Microbiol. Immunol. 137: 216–222

  • Stella MC, Comoglio PM . 1999 Int. J. Biochem. Cell. Biol. 31: 1357–1362

  • Takeuchi T, Harris JL, Huang W, Yan KW, Couglin SR, Craik CS . 2000 J. Biol. Chem. 275: 26333–26342

  • Takeuchi T, Shuman MA, Craik CS . 1999 Proc. Natl. Acad. Sci. USA 96: 11054–11061

  • Tang BL . 2001 Int. J. Biochem. Cell. Biol. 33: 33–44

  • Tanimoto H, Underwood LJ, Wang Y, Shigemasa K, Parmley TH, O'Brien TJ . 2001 Tumour. Biol. 22: 104–114

  • Turk B, Turk D, Turk V . 2000 Biochim. Biophys. Acta 1477: 98–111

  • Vu TH, Werb Z . 2000 Genes Dev. 14: 2123–2133

  • Werb Z . 1997 Cell 91: 439–442

  • Werb Z, Vu TH, Rinkenberger JL, Coussens LM . 1999 Apmis 107: 11–18

  • Williams O, Brady HJ . 2001 Trends Immunol. 22: 107–111

  • Yamada K, Takabatake T, Takeshima K . 2000 Gene 252: 209–216

  • Yamazaki M, Tsuboi R, Lee YR, Ishidoh K, Mitsui S, Ogawa H . 1999 J. Investig. Dermatol. Symp. Proc. 4: 312–315

  • Yan W, Wu F, Morser J, Wu Q . 2000 Proc. Natl. Acad. Sci. USA 97: 8525–8529

  • Zhang Y, Cai X, Schlegelberger B, Zheng S . 1998 Cytogenet. Cell Genet. 83: 56–57

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Acknowledgements

We thank the NIDCR gene targeting core for blastocyst injections, Drs Henning Birkedal-Hansen, Silvio Gukind, Kenn Holmbeck, Keld Danø, and Mary Jo Danton for critically reading the manuscript, Dr Panomwat Amornphimoltam for advice on keratin immunostaining, and Dr Ulrike Lichti for advice on hair canal formation. We also thank Yamei Gao, Elizabeth Smith, Hannah Aaronson, and David Mitola for their excellent technical assistance. K List was supported by fellowships from the Danish Cancer Society and Svend Cole Frederiksen and Hustrus Foundation.

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Authors and Affiliations

  1. Oral and Pharyngeal Cancer Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, 30 Convent Drive, Bethesda, 20892, Maryland, MD, USA

    Karin List, Roman Szabo, Lars H Engelholm & Thomas H Bugge

  2. Oral Infection and Immunity Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, 30 Convent Drive, Bethesda, 20892, Maryland, MD, USA

    WanJun Chen & Sharon M Wahl

  3. Cellular Imaging Core, National Institutes of Dental and Craniofacial Research, National Institutes of Health, 30 Convent Drive, Bethesda, 20892, Maryland, MD, USA

    William Swaim

  4. Finsen Laboratory, Strandboulevarden 49, Copenhagen, DK-2100, Denmark

    Karin List, Lars H Engelholm & Niels Behrendt

  5. Department of Experimental Pathology, American Red Cross, 15601 Crabbs Branch Way, Rockville, 20855, Maryland, MD, USA

    Christian C Haudenschild

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  1. Karin List
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Correspondence to Thomas H Bugge.

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List, K., Haudenschild, C., Szabo, R. et al. Matriptase/MT-SP1 is required for postnatal survival, epidermal barrier function, hair follicle development, and thymic homeostasis. Oncogene 21, 3765–3779 (2002). https://doi.org/10.1038/sj.onc.1205502

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