The roles of p53 and p21 in normal development and hyperthermia‐induced malformations

Abstract

Our study confirms that p53 plays a role in normal development and has shown, for the first time that p53 and p21 function to suppress HS-induced malformations.

Two distinct knockout approaches highlight a critical role for p53 in rat development

“…2b). Although these two abnormalities are the most prevalent NTDs, spina bifida in p53 mutant mice has only been reported in one study28. Exencephaly was only found in the female embryos, consistent with previous observations of a higher incidence of NTDs in human females and in numerous mouse models29.…”

Inducible 70 kDa heat shock proteins protect embryos from teratogen‐induced exencephaly: Analysis using Hspa1a/a1b knockout mice

“…In addition, it is important to identify other suppressors of teratogenic effects. Recent work from our laboratory has shown that p53, a key cellular regulator that determines whether a cell will arrest or die in response to a variety of stresses, also suppresses hyperthermia-induced exencephaly in mouse fetuses (Hosako et al, 2009). Although far from conclusive, our finding that HSPa1a/a1b and p53, both of which are known to regulate the apoptotic pathway, function as suppressors of teratogenic effects suggests that apoptosis is causally linked to the failure of neural tube closure and the development of exencephaly in hyperthermiatreated embryos.…”

Mutations in Lyar and p53 are synergistically lethal in female mice

“…Neural tube defects (NTDs), including spina bifida and anencephaly, result from impaired neural tube closure during early embryogenesis and are among the most serious congenital malformations in humans. Periconceptional folic acid supplementation has contributed to a decline in NTD frequency (Honein et al,2001); however, the occurrence of NTDs remains high with a frequency between 1 and 20 per 1000 births depending on geographical location (Olney and Mulinare,2002). The etiology of NTDs has not been fully elucidated and is thought to be multifactorial, with contributions from both gene‐gene and gene‐environment interactions.…”