Metastasis-promoting Mts1(S100A4) protein belongs to the S100 family of 
Ca(2+)-binding proteins. A mouse strain with a germ-line inactivation of the 
S100A4 gene was generated. The mice were viable and did not display 
developmental abnormalities in the postnatal period. However, an abnormal sex 
ratio was observed in the litters with the S100A4-/- genotype, raising the 
possibility of a certain level of embryonic lethality in this strain. In all, 
10% of 10-14-month-old S100A4-null animals developed tumors. This is a 
characteristic feature of mouse strains with inactivated tumor suppressor genes. 
Spontaneous tumors of S100A4-/- mice were p53 positive. Recently, we have shown 
that S100A4 interacts with p53 tumor suppressor protein and induces apoptosis. 
We proposed that impairment of this interaction could affect the 
apoptosis-promoting function of p53 that is involved in its tumor suppressor 
activity. The frequency of apoptosis in the spleen of S100A4-/- animals after 
whole-body gamma-irradiation was reduced compared to the wild-type animals. The 
same was true for the transcriptional activation of the p53 target genes - 
waf/p21/cip1 and bax. Taken together, these observations indicate that 
spontaneous tumors in S100A4-/- mice are a result of functional destabilization 
of p53 tumor suppressor gene.