Table 1.
Bcl2 gene family knockout mouse phenotypes.
| Genotype | Systemic Phenotype | Retinal Phenotypea | Neuroprotective?b | References |
|---|---|---|---|---|
| Pro-Apoptotic | ||||
| Bax−/− | Viable, Male infertility | Supernumerary GCL, INL, Photoreceptors unaffected |
Yes | (Knudson et al., 1995; Li et al., 2000) |
| Bak−/− | Viable | None | Noc | (Lindsten et al., 2000) |
| Bax−/−/Bak−/− | High perinatal mortality, CNS/reproductive abnormalities, Increased myeloid and lymphoid cells |
Photoreceptors are protected from light damage |
Not testedd | (Hahn et al., 2004; Lindsten et al., 2000) |
| Bok−/− | Viable, Female has increased thymus and spleen weight |
None | Not tested | (Ke et al., 2012) |
| Anti-Apoptotic | ||||
| Bcl2−/− | Early postnatal mortality | n/a | n/a | (Veis et al., 1993) |
| Bcl-x−/− | Embryonic lethal | n/a | n/a | (Motoyama et al., 1995) |
| Bcl-w−/− | Viable, Male infertility | None | Not tested | (Print et al., 1998; Ross et al., 1998) |
| Mcl1−/− | Peri-implantation embryonic lethal | n/a | n/a | (Rinkenberger et al., 2000) |
| A1−/− | Viable, Increased neutrophil apoptosis | Unknown | Not tested | (Hamasaki et al., 1998) |
| BH3-only | ||||
| Bad−/− | Viable, Develop diffuse large B cell lymphoma | Unknown | Not tested | (Ranger et al., 2003) |
| Bid−/− | Viable, Resistant to Fas-induced hepatocellular apoptosis, Aged mice develop myeloid hyperplasia then malignancy |
None | No | (Harder and Libby, 2011; Harder and Libby, 2013; Yin et al., 1999; Zinkel et al., 2003) |
| Bik−/− | Viable | Unknown | Not tested | (Coultas et al., 2004) |
| Bim−/− | Viable, Accumulation of myeloid and lymphoid cells, Aged mice develop autoimmune kidney disease |
Increased retinal vasculature, Developmental abnormalities in optic nerve head |
Partial | (Bouillet et al., 1999; Harder et al., 2012b) |
| Bmf−/− | Viable, Develop B-cell restricted lymphadenopathy | Unknown | Not tested | (Labi et al., 2008) |
| Hrk(Dp5)−/− | Viable | Unknown | No | (Fernandes et al., 2013; Imaizumi et al., 2004) |
| Noxa−/− | Viable, Motor neurons protected after axotomy | Unknown | Not tested | (Kiryu-Seo et al., 2005; Villunger et al., 2003) |
| Puma(Bbc3)−/− | Viable | Supernumerary | No | (Harder and Libby, 2011; Villunger et al., 2003) |
| Bim−/−/Bid−/− | Viable | None | No | (Harder and Libby, 2013) |
|
Bim−/− Puma−/− |
Viable, enlarged lymph node and spleen, thymic hyperplasia |
Supernumerary | Partial | (Erlacher et al., 2006; Harder and Libby, 2013) |
| Bid−/−/Puma−/− | Viable | Supernumerary | No | (Harder and Libby, 2013) |
|
Bim−/−/Bid−/− Puma−/− |
Viable | Supernumerary | Partial | (Harder and Libby, 2013) |
| Bim−/−/Hrk−/− | Viable | None | No | (Fernandes et al., 2013) |
a
Designations of not/applicable (n/a) refer to mice that cannot be tested because the deletion is embryonic lethal. Designations of Unknown refer to no citations regarding a retinal phenotype in relevant mice.
b
Designations of n/a are the same as for the column on retinal phenotype. Designations of Not Tested refer to no neuroprotective study having been conducted using these mice.
c
Nickells et al., unpublished.
d
Neurons express a splice variant of Bak that disables the full-length protein (Uo et al., 2005). It is expected that neurons in Bax-deficient mice essentially have a Bax−/−/Bak−/− genotype.