Table 1.
Human genetic syndromes with p53-dependent developmental phenotypes in mouse models.
| Human syndrome | Elevated p53 levels in human patient tissue/cells | Mouse model | ||
|---|---|---|---|---|
| Genotype | Developmental defects rescued by loss of p53a | References | ||
| Treacher Collins syndrome | N/D | Tcof1+/− | Frontonasal hypoplasia, cleft palate, microphthalmia, cranial nerve defects, neonatal lethality | Jones et al. (2008) |
| Diamond–Blackfan anemia | Yes (Dutt et al., 2011; Aspesi et al., 2017) | Rps7Zma/+ | Erythrocyte maturation delay, tail kink, white belly spot, developmental delay | Watkins-Chow et al. (2013) |
| Rps19Dsk3/+ | Lower red blood cell count, skin hyperpigmentation, reduced postnatal body weight | McGowan et al. (2008) | ||
| 5q− syndrome | Yes (Pellagatti et al. 2010; Dutt et al. 2011) | Deletion spanning Rps14 | Decreased number of hematopoietic stem cells | Barlow et al. (2010) |
| Fanconi anemia | Yes (Ceccaldi et al., 2012) | Fancd2−/− | Decreased number of hematopoietic stem cells | Ceccaldi et al. (2012) |
| Xrcc2−/− | Short tail, lethality ~E12.5 | Adam et al. (2007) | ||
| Rad51−/− | Lethality ~E6.5 | Lim and Hasty (1996) | ||
| Brca1Δ11/Δ11 | Late gestational lethality | Xu et al. (2001) | ||
| Wnt1-Cre;Brca1flox/flox | Hypoplastic craniofacial skeleton | Kitami et al. (2018) | ||
| Tyr-Cre;Brca1flox/flox | Piebald fur pigmentation | Tonks et al. (2012) | ||
| Palb2−/− | Lethality ~E8.5 | Bouwman et al. (2011) | ||
| Autosomal recessive primary microcephaly | N/D | Math1-Cre;Aspmflox/flox | Hypoplastic cerebellum | Williams et al. (2015) |
| Cit−/− | Microcephaly, ataxia | Bianchi et al. (2017) | ||
| Cenpj−/− | Lethality ~E9.5 | Bazzi and Anderson (2014) | ||
| Nestin-Cre;Cenpjflox/flox | Microcephaly | Insolera et al. (2014) | ||
| Seckel syndrome | N/D | Cep63T/T | Microcephaly | Marjanović et al. (2015) |
| Nijmegen breakage syndrome | Yes (Mlody et al., 2017) | Nestin-Cre;Nbnflox/flox | Microcephaly, cerebellar defects, ataxia, postnatal growth retardation | Frappart et al. (2005) |
| LIG4 syndrome | N/D | Lig4−/− | Late gestational lethality | Frank et al. (2000) |
| SSMED | N/D | Xrcc4−/− | Late gestational lethality | Gao et al. (2000) |
| Microlissencephaly | N/D | Nde1−/− | Microcephaly | Houlihan and Feng (2014) |
| Richieri–Costa–Pereira syndrome | N/D | Emx1-Cre; Eif4a3flox/+ | Microcephaly | Mao et al. (2016) |
| Thrombocytopenia-absent radius syndrome | N/D | Emx1-Cre; Rbm8aflox/+ | Microcephaly | Mao et al. (2016) |
| Waardenburg syndrome type 1 | N/D | Pax3Sp/Sp | Neural tube defects, heart outflow tract defects | Morgan et al. (2008), Pani (2002) |
| 22q11.2 deletion syndrome | N/D | Tbx1neo2/− | Pharyngeal arch artery defects, heart outflow tract defects | Caprio and Baldini (2014) |
| CHARGE syndrome | Yes (Van Nostrand et al., 2014) | Chd7−/− | Lethality ~E10.5 | Van Nostrand et al. (2014) |
| Dyskeratosis congenita | Yes (Pereboeva et al., 2016) | AcdAcd/Acd | Skin hyperpigmentation, hypoplastic adrenal glands, hindlimb hypoplasia, vertebral fusions | Else et al. (2009), Vlangos et al. (2009) |
| Terc−/− | Hypoplastic testes | Chin et al. (1999) | ||
aIncludes developmental defects that are fully or partially rescued by concomitant deletion of one or both alleles of Trp53.