Expression profiling in knockout mice: lymphotoxin versus tumor necrosis factor in the maintenance of splenic microarchitecture.
Expression profiling provides a powerful approach to define the underlying molecular mechanisms in disease. Several techniques referred collectively to as gene profiling may be also helpful in the analysis of the phenotype of mice with targeted mutations, especially if applied to distinct histological compartments, to specific cell types or to evaluate the effect of specific challenges, such as infection. Here we review several of the existing techniques applicable to genetic knockout studies, and share our experience from the study of mice with tumor necrosis factor (TNF) and lymphotoxin (LT) deficiencies, with specific emphasis on the distinction between TNF- and LT-mediated signalling pathways in vivo. Gene expression profiling analysis of TNF/LT-deficient mice supports the notion that TNF and LT, originally discovered as distinct biological activities, manifest both distinct and redundant functions in vivo.
Shakhov
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Intramural Research Support Program, SAIC Frederick, Division of Basic Sciences, Building 560, Room 31-33, NCI-FCRDC, PO Box B, Frederick, MD 21702, USA. shakhova@mail.ncifcrf.gov
Nedospasov
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SA
D000818:Animals; D000954:Antigens, Surface; D002135:Calcium-Binding Proteins; D018925:Chemokines / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins; D020869:Gene Expression Profiling / Q000379:methods; D054501:Group II Phospholipases A2; D008214:Lymphocytes / Q000378:metabolism; D008233:Lymphotoxin-alpha / Q000235:genetics* / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008894:Milk Proteins; D009077:Mucins / Q000235:genetics / Q000378:metabolism; D010741:Phospholipases A / Q000235:genetics / Q000378:metabolism; D011971:Receptors, Immunologic / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D013154:Spleen / Q000473:pathology / Q000502:physiology* / Q000648:ultrastructure; D014409:Tumor Necrosis Factor-alpha / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism; D025521:Tumor Suppressor Proteins
D000954:Antigens, Surface; D002135:Calcium-Binding Proteins; D018925:Chemokines; D004268:DNA-Binding Proteins; C114202:Dmbt1 protein, mouse; D008233:Lymphotoxin-alpha; C490460:MARCO protein, human; C092228:Marco protein, mouse; D008562:Membrane Glycoproteins; C490919:Mfge8 protein, mouse; D008894:Milk Proteins; D009077:Mucins; D011971:Receptors, Immunologic; D014409:Tumor Necrosis Factor-alpha; D025521:Tumor Suppressor Proteins; D010741:Phospholipases A; D054501:Group II Phospholipases A2