Targeted disruption of the mouse transforming growth factor-beta 1 gene results in multifocal inflammatory disease.
Transforming growth factor-beta 1 (TGF-beta 1) is a multifunctional growth factor that has profound regulatory effects on many developmental and physiological processes. Disruption of the TGF-beta 1 gene by homologous recombination in murine embryonic stem cells enables mice to be generated that carry the disrupted allele. Animals homozygous for the mutated TGF-beta 1 allele show no gross developmental abnormalities, but about 20 days after birth they succumb to a wasting syndrome accompanied by a multifocal, mixed inflammatory cell response and tissue necrosis, leading to organ failure and death. TGF-beta 1-deficient mice may be valuable models for human immune and inflammatory disorders, including autoimmune diseases, transplant rejection and graft versus host reactions.
Shull
M M
MM
Department of Molecular Genetics, Biochemistry, and Microbiology, University of Cincinnati College of Medicine, Ohio 45267-0524.
Ormsby
I
I
Kier
A B
AB
Pawlowski
S
S
Diebold
R J
RJ
Yin
M
M
Allen
R
R
Sidman
C
C
Proetzel
G
G
Calvin
D
D
D000818:Animals; D001483:Base Sequence; D016207:Cytokines / Q000235:genetics; D015870:Gene Expression; D005796:Genes; D006720:Homozygote; D007249:Inflammation / Q000235:genetics* / Q000473:pathology; D007958:Leukocyte Count; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D016254:Mutagenesis, Insertional; D009336:Necrosis; D009838:Oligodeoxyribonucleotides / Q000737:chemistry; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics; D015183:Restriction Mapping; D016212:Transforming Growth Factor beta / Q000502:physiology*
D016207:Cytokines; D009838:Oligodeoxyribonucleotides; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta