Table 1.
Effect of global and conditional Adam10 deletion on gastrointestinal tract function and pathophysiology
| ADAM10- deficient mouse models |
Tissue distribution | Experimental model |
Gastrointestinal phenotype |
Notch rescue |
Reference(s) |
|---|---|---|---|---|---|
| Null | |||||
| Adam10−/− | Global | Development | Embryonic lethal at E9.5; lethality prior to gastrointestinal development |
ND | 51 |
| IEC specific | |||||
|
Villin-Cre; Adam10flox/flox |
All IECs at ~ E15 | IEC development | Postnatal lethal atP1; ↓crypt cell proliferation, ↑secretory cell differentiation |
Yes | 50 |
|
Villin-CreER; Adam10flox/flox |
All IECs | Adult IEC homeostasis |
Lethality; ↓ISC markers, e.g., Olfm4, ↓crypt cell proliferation, ↑secretory cell differentiation |
Yes | 50 |
|
Cdx2P-CreER; Adam10flox/flox |
IECs in distal ileum, cecum, and colon |
APCflox/flox model | No adenoma initiation | Yes | 135 |
|
Lgr5-CreER; Adam10flox/flox |
Lgr5+ CBCs | ISC niche, crypt homeostasis |
Loss of Adam10-deficient Lgr5+ CBCs |
Yes | 50 |
| APCflox/flox model | No adenoma initiation | Yes | 135 | ||
|
Bmi1-CreER; Adam10flox/flox |
Bmi1+ cells | ISC niche, crypt homeostasis |
Loss of Adam10-deficient Bmi1+ ISCs |
Yes | P.J. Dempsey, unpublished observation |
|
Defensin4-Cre; Adam10flox/flox |
Paneth cells | Paneth cell biology | No overt phenotype | ND | P.J. Dempsey, M. Rajala &M.J. Myers Jr., unpublished observation |
|
Cryptidin2- dnAdam10 |
Paneth cells | Paneth cell biology | Mislocalization of Paneth cells |
ND | 63 |
| Leukocyte specific | |||||
|
PolyIC Mx-Cre; Adam10flox/flox |
Broad expression, hematopoietic cells |
Hematopoiesis | Enlarged liver with thrombocytosis and myeloid/granulocyte infiltration |
ND | 150, 151 |
| Increased mast cell infiltration in small intestine |
152 | ||||
|
CD19-Cre; Adam10flox/flox |
B cells | B cell development | Disturbed secondary lymphoid organ architecture, including Peyer’s patches, as a result of a compensatory increase in ADAM17/TNFα signaling axis |
ND | 21, 153, 154 |
|
LysM-CreER; Adam10flox/flox |
Neutrophils, monocytes, macrophages |
Inflammation models |
LPS TLR4-induced inflammatory polarization of macrophages |
ND | 128, 129 |
| DSS colitis | Severe, unremitting inflammation |
Yes | 129 | ||
Abbreviations: CBCs, crypt base columnar stem cells; DSS, dextran sodium sulfate; E, embryonic day; IEC, intestinal epithelial cell; ISC, intestinal stem cell; LPS, lipopolysaccharide; ND, not determined; P, postnatal day.