Table 2.
Phenotypic characteristics of Gadd45 knockout mice.
| Targeted Gadd45 member | Observed phenotype | Reference |
|---|---|---|
| Gadd45α−/− | Genomic instability, abnormal nucleotide- and base-excision DNA repair, increased sensitivity to carcinogenesis | Hollander et al. (1999, 2001), Tront et al. (2006), Maeda et al. (2005) |
| Impaired ability for cell differentiation and increased sensitivity to the induction of apoptosis | Gupta et al. (2006) | |
| Increased sensitivity to skin irradiation | Hildesheim et al. (2002) | |
| Premature death, auto-immunity | Salvador et al. (2002) | |
| Abnormal hematopoiesis | Salvador et al. (2002), Gupta et al. (2005) | |
| Depletion of stem cell pool; decreased clonogenic potential of myeloid progenitors | Hoffman and Liebermann (2007) | |
| Nervous, reproductive and renal disorders | Hollander et al. (1999), Salvador et al. (2002) | |
| Double KO: Gadd45α−/−, XPC−/− | Premature death and increased tumorigenesis | Hollander et al. (2005) |
| Double KO: Gadd45α−/−, Cdkn1a−/− | Premature death, auto-immunity, abnormal hematopoiesis, impaired homeostasis, renal disorders | Salvador et al. (2002) |
| Abnormal chromosome number, increased cell proliferation | Hollander et al. (1999) | |
| Decreased cellular sensitivity to ultraviolet irradiation, normal nucleotide-excision repair | Maeda et al. (2005) | |
| Double KO: Gadd45α−/−, Brca1−/− | Exencephaly at embryonic days 9.5–10.5, complete prenatal lethality | Wang et al. (2004) |
| Gadd45β−/− | Impaired immunity and anti-tumor immune response; increased susceptibility to ionizing radiation and chemical carcinogens | Ju et al. (2009), Lu et al. (2004) |
| Autoimmune conditions | Liu et al. (2005) | |
| Impaired ability for differentiation and increased sensitivity to the induction of apoptosis | Gupta et al. (2006) | |
| Abnormal hematopoiesis | Gupta et al. (2005) | |
| Depletion of stem cell pool; decreased clonogenic potential of myeloid progenitors | Hoffman and Liebermann (2007) | |
| Gadd45γ−/− | Impaired immunity | Lu et al. (2001), Lu et al. (2004) |
| Normal hematopoiesis and proliferative response to IL-2 | Hoffmeyer et al. (2001) | |
| Abnormal cell physiology | Cai et al. (2006) | |
| Double KO: Gadd45β−/−, Gadd45γ−/− | Impaired immunity and anti-tumor immune response; Autoimmune conditions |
Ju et al. (2009), Lu et al. (2004) Liu et al. (2005) |
| Triple KO: Gadd45α−/−, Gadd45β−/−, Gadd45γ−/− | Increased cell proliferation in the renal outer medullary cells | Cai et al. (2006) |
| Ras-over expressing mice: Gadd45α+/− or Gadd45α−/− | Ras-driven breast tumorigenesis is Gadd45α-dependent; Gadd45α inhibits the onset and growth of mammary tumors | Tront et al. (2006) |