Table 2.

Bcl2l1 (Bcl-x) gene targeting in mice.

Mouse model	Targeted tissue/cell population	Findings	Reference
constitutive Bcl-x-/-	whole body	embryonic lethal (E13.5) BCL-XL is essential for the survival of erythroid progenitor cells and catecholaminergic neuronal cells	[46]
haematopoietic chimaeras that were produced by microinjection of Bcl-x-/- ES cells into Rag2-/- blastocysts	T cells (DN stage) B cells (pro B stage)	viable BCL-XL is dispensable for the survival of lymphocyte progenitors but the survival of DP thymocytes is compromised upon loss of BCL-XL	[93]
chimaeras (microinjection of Bcl-x-/- ES cells in wt blastocysts)	whole body	viable offspring with >80% chimaerism BCL-XL is essential for the survival of primitive and definitive erythroid progenitors	[45]
Bcl-x hypomorphic mouse (introduction of a loxP flanked neomycin (neo) cassette into the promoter of Bcl-x)	whole body	viable BCL-XL is essential for the survival of mouse germ cells during gonadogenesis in males and females	[63]
MMTV-Cre-Bcl-xfl/fl	erythroid cells	mice die ~3 months after birth due to severe haemolytic anaemia and splenomegaly BCL-XL is essential for the survival of erythroid cells at the end of their maturation	[99]
MMTV-Cre-Bcl-xfl/fl WAP-Cre- Bcl-xfl/fl	mammary epithelium	viable BCL-XL is not essential during mammopoiesis, but critical for controlled apoptosis during the first phase of involution	[155]
AlbCre-Bcl-x	hepatocytes	viable but mice develop severe liver fibrosis 5-7 months after birth BCL-XL is essential for hepatocyte survival	[65]
pCMV-Cre via gene gun delivery to the abdomnen of Bcl-xfl/fl mice	dendritic cells	viable BCL-XL is essential for the survival of certain dendritic cell populations	[73, 156]
LckCre- Bcl-xfl/fl	T lymphoid cells	viable BCL-XL is not essential for the survival of effector and memory T lymphocytes	[94]
tyrosine hydroxylaseCre-Bcl-xfl/fl	a subset of CNS neurons catecholaminergic neurons	viable BCL-XL is required for proper development of the mouse substantia nigra (catecholaminergic neuronal population reduced by one-third upon induced Bcl-x deletion)	[49]
Bcl-xPlt16/Plt16 Bcl-xPlt20/Plt20 (destabilising point mutations)	whole body	Only few Bcl-xPlt16/Plt16 mice found at birth Bcl-xPlt20/Plt20 mice are viable anaemia/hyperplasia of erythroid progenitors BCL-XL is essential for normal platelet lifespan	[100]
RIP-Cre-Bcl-xfl/fl	pancreatic β-cells	viable BCL-XL is dispensable during islet development in the mouse but Bcl-x-/- β-cells are hypersensitive to apoptotic stimuli	[66]
Sftpc-Cre-Bcl-xfl/fl	epithelial cell	perinatally lethal in approximately 50% of the expected offspring BCL-XL is not essential for proper lung development in viable offspring but respiratory epithelial cells are hypersensitive to apoptotic stimuli	[67]
Pf4Cre-Bcl-xfl/fl	megakaryocyte lineages	mice present with severe thrombocytopenia ~7 weeks after birth BCL-XL is essential for megakaryocyte function to produce platelets but dispensable for their growth and survival	[101]
Pf4Cre-Bcl-xfl/fl-Mcl-1fl/fl	megakaryocyte lineages	BCL-XL is essential for megakaryocyte survival in combination with MCL-1	[102, 103]
RosaCreERT2-Bcl-xfl/fl	CreERT2-induced whole body deletion	Mice die ~25 days after CreERT2-induced Bcl-x deletion due to severe anaemia and thrombocytopenia BCL-XL is critical for the survival of red blood cells and platelets	[64]
wt BM chimaera; RosaCreERT2-Bcl-xfl/fl host	CreERT2-induced deletion only in the non-haematopoietic cells	Mice die ~30 days after CreERT2-induced Bcl-x deletion due to severe kidney damage and secondary anaemia and thrombocytopenia BCL-XL is critical for the survival of renal tubular epithelial cells	[64]