Ulcerative colitis and adenocarcinoma of the colon in G alpha i2-deficient mice.
G proteins are involved in cellular signalling and regulate a variety of biological processes including differentiation and development. We have generated mice deficient for the G protein subunit alpha i2 (G alpha i2) by homologous recombination in embryonic stem cells. G alpha i2-deficient mice display growth retardation and develop a lethal diffuse colitis with clinical and histopathological features closely resembling ulcerative colitis in humans, including the development of adenocarcinoma of the colon. Prior to clinical symptoms, the mice show profound alterations in thymocyte maturation and function. The study of these animals should provide important insights into the pathogenesis of ulcerative colitis as well as carcinogenesis.
Rudolph
U
U
Department of Cell Biology, Baylor College of Medicine, Houston, Texas 77030, USA.
Finegold
M J
MJ
Rich
S S
SS
Harriman
G R
GR
Srinivasan
Y
Y
Brabet
P
P
Boulay
G
G
Bradley
A
A
Birnbaumer
L
L
D000230:Adenocarcinoma / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D000595:Amino Acid Sequence; D000818:Animals; D015703:Antigens, CD / Q000032:analysis; D001483:Base Sequence; D002874:Chromosome Mapping; D003093:Colitis, Ulcerative / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D003110:Colonic Neoplasms / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D016207:Cytokines / Q000032:analysis; D005260:Female; D051960:GTP-Binding Protein alpha Subunit, Gi2; D019206:GTP-Binding Protein alpha Subunits, Gi-Go; D019204:GTP-Binding Proteins / Q000235:genetics*; D005804:Genes, Lethal; D006720:Homozygote; D007136:Immunoglobulins / Q000032:analysis; D008214:Lymphocytes / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D008957:Models, Genetic; D008969:Molecular Sequence Data; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D013047:Specific Pathogen-Free Organisms / Q000235:genetics / Q000502:physiology; D013154:Spleen / Q000276:immunology; D013950:Thymus Gland / Q000276:immunology
D015703:Antigens, CD; D016207:Cytokines; D007136:Immunoglobulins; D011518:Proto-Oncogene Proteins; D019204:GTP-Binding Proteins; D051960:GTP-Binding Protein alpha Subunit, Gi2; D019206:GTP-Binding Protein alpha Subunits, Gi-Go; C498016:Gnai2 protein, mouse