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

TY - JOUR

T1 - Matriptase/MT-SP1 is required for postnatal survival, epidermal barrier function, hair follicle development, and thymic homeostasis

AU - List, Karin

AU - Haudenschild, Christian C

AU - Szabo, Roman

AU - Chen, WanJun

AU - Wahl, Sharon M

AU - Swaim, William

AU - Engelholm, Lars H

AU - Behrendt, Niels

AU - Bugge, Thomas H.

PY - 2002/5/23

Y1 - 2002/5/23

N2 - 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.

AB - 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.

KW - Amino Acid Sequence

KW - Animals

KW - Animals, Newborn

KW - Apoptosis

KW - Base Sequence

KW - Epidermis

KW - Female

KW - Gene Deletion

KW - Genes, Lethal

KW - Hair Follicle

KW - Homeostasis

KW - Male

KW - Membrane Proteins

KW - Mice

KW - Mice, Knockout

KW - Microscopy, Electron, Scanning

KW - Molecular Sequence Data

KW - Permeability

KW - RNA, Messenger

KW - Reverse Transcriptase Polymerase Chain Reaction

KW - Serine Endopeptidases

KW - Skin Abnormalities

KW - Survival Rate

KW - Thymus Gland

KW - Trypsin

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.1038/sj.onc.1205502

DO - 10.1038/sj.onc.1205502

M3 - Journal article

C2 - 12032844

SN - 0950-9232

VL - 21

SP - 3765

EP - 3779

JO - Oncogene

JF - Oncogene

IS - 23

ER -