Gene profiling approach in the analysis of lymphotoxin and TNF deficiencies.
Mice with combined lymphotoxin-alpha (LTalpha) and tumor necrosis factor (TNF) deficiencies show defects in the structure of peripheral lymphoid organs such as spleen, lymph nodes, and gut-associated lymphoid tissues. To identify genes associated with this defective phenotype in spleen, we applied a gene profiling approach, including subtractive cloning and gene array hybridizations, to mice with combined TNF/LT deficiency. The differentially expressed genes identified by these techniques was then evaluated by Northern blot analysis for splenic expression in knockout mice with single LTalpha or single TNF deficiency. Most of the genes detected in this analysis are directly or indirectly associated with disrupted LT and not TNF signaling.
Intramural Research Support Program, SAIC Frederick and Laboratory of Molecular Immunoregulation, Division of Basic Sciences, NCI-FCRDC, Maryland 21702, USA. shakhova@mail.ncifcrf.gov
A N
AN
Shakhov
I G
IG
Lyakhov
A V
AV
Tumanov
A V
AV
Rubtsov
L N
LN
Drutskaya
M W
MW
Marino
S A
SA
Nedospasov
D000818:Animals; D015815:Cell Adhesion Molecules / Q000096:biosynthesis / Q000235:genetics; D018925:Chemokines / Q000096:biosynthesis / Q000235:genetics; D018076:DNA, Complementary / Q000235:genetics; D020224:Expressed Sequence Tags; D020869:Gene Expression Profiling / Q000379:methods; D005786:Gene Expression Regulation; D054501:Group II Phospholipases A2; D008221:Lymphoid Tissue / Q000473:pathology*; D008233:Lymphotoxin-alpha / Q000235:genetics*; D008565:Membrane Proteins / Q000096:biosynthesis / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009504:Neutrophils / Q000378:metabolism; D009693:Nucleic Acid Hybridization; D020411:Oligonucleotide Array Sequence Analysis; D009928:Organ Specificity; D010179:Pancreas / Q000201:enzymology; D010641:Phenotype; D010741:Phospholipases A / Q000096:biosynthesis / Q000235:genetics / Q000302:isolation & purification; D019707:Receptors, Chemokine / Q000096:biosynthesis / Q000235:genetics; D013047:Specific Pathogen-Free Organisms; D013154:Spleen / Q000378:metabolism* / Q000473:pathology; D013382:Subtraction Technique; D014409:Tumor Necrosis Factor-alpha / Q000172:deficiency* / Q000235:genetics
D015815:Cell Adhesion Molecules; D018925:Chemokines; D018076:DNA, Complementary; D008233:Lymphotoxin-alpha; D008565:Membrane Proteins; D019707:Receptors, Chemokine; D014409:Tumor Necrosis Factor-alpha; D010741:Phospholipases A; D054501:Group II Phospholipases A2