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Molecular and Cellular Biology, June 2004, p. 5304-5313, Vol. 24, No. 12
0270-7306/04/$08.00+0     DOI: 10.1128/MCB.24.12.5304-5313.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Diet-Induced Obesity and Reduced Skin Cancer Susceptibility in Matrix Metalloproteinase 19-Deficient Mice

Alberto M. Pendás,1* Alicia R. Folgueras,1 Elena Llano,1,{dagger} John Caterina,2 Françoise Frerard,3 Francisco Rodríguez,1 Aurora Astudillo,4 Agnès Noël,3 Henning Birkedal-Hansen,2 and Carlos López-Otín1

Departamento de Bioquímica y Biología Molecular, Facultad de Medicina, Instituto Universitario de Oncología, Universidad de Oviedo, and,1 Servicio de Anatomía Pathológica, Hospital Central de Asturias,Oviedo, Spain,4 MMP Unit, National Institute of Dental and Craniofacial Research, Bethesda, Maryland 20892,2 Laboratory of Tumor and Developmental Biology, Universite de Liège, B-4000 Liège, Belgium3

Received 22 March 2004/ Accepted 26 March 2004

Matrix metalloproteinase 19 (MMP-19) is a member of the MMP family of endopeptidases that, in contrast to most MMPs, is widely expressed in human tissues under normal quiescent conditions. MMP-19 has been found to be associated with ovulation and angiogenic processes and is deregulated in diverse pathological conditions such as rheumatoid arthritis and cancer. To gain further insights into the in vivo functions of this protease, we have generated mutant mice deficient in Mmp19. These mice are viable and fertile and do not display any obvious abnormalities. However, Mmp19-null mice develop a diet-induced obesity due to adipocyte hypertrophy and exhibit decreased susceptibility to skin tumors induced by chemical carcinogens. Based on these results, we suggest that this enzyme plays an in vivo role in some of the tissue remodeling events associated with adipogenesis, as well as in pathological processes such as tumor progression.

* Corresponding author. Mailing address: Departamento de Bioquímica y Biología Molecular, Facultad de Medicina, Universidad de Oviedo, 33006 Oviedo, Spain. Phone: 34-985-104201. Fax: 34-985-103564. E-mail: amp{at}correo.uniovi.es.

{dagger} Present address: Centro Nacional de Investigaciones Oncológicas, Madrid, Spain.

Molecular and Cellular Biology, June 2004, p. 5304-5313, Vol. 24, No. 12
0022-538X/04/$08.00+0     DOI: 10.1128/MCB.24.12.5304-5313.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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