Sequence variants of p21 gene of the MRL/MpJ mouse: a possible association with the deficit of p21 protein and regenerative phenotype. - Publikacja - MOST Wiedzy

Wyszukiwarka

Sequence variants of p21 gene of the MRL/MpJ mouse: a possible association with the deficit of p21 protein and regenerative phenotype.

Abstrakt

The MRL/MpJ mouse is known for its enhanced regeneration abilities that manifested themselves by scarless ear-hole wound closure. The deficit of p21 found in the MRL is associated with the regenerative capacity as the p21 gene knockout in a mouse strain unrelated to the MRL mouse results in an ear-hole closure effect, similar to that observed in the MRL mouse. Cdkn1a gene encodes p21 protein, a cyclin-dependent kinase inhibitor, which plays an important role in cell cycle regulation. By interacting with CDKs it may stop cell cycle progression at different stages. The p21 gene expression may be initiated from two independent promoters, the classical and the p53-induced one, what is important in case of DNA damage. The cell cycle profile of fibroblast-like cells derived from the MRL mouse shows accumulation in the G2 phase and is different from the profile of the non-regenerative C57BL/6J (B6) mouse. This observation has been explained by the deficit of p21 that causes G1/M cell cycle checkpoint deficiency that results in the uncontrolled entrance into the S phase, which entails the replication stress that involves the endogenous DNA damage. Moreover p21 is not detected in the MRL tissues, even after γ-irradiation, although p53, which up-regulates p21 expression after DNA damage, is constantly present. In our research, we have attempted to investigate the genetic background of p21 deficiency in the MRL mouse. We sequenced the p21 gene of the MRL mouse and compared its nucleotide sequence with 17 already known gene sequences of other laboratory murine strains. We identified a few nucleotide sequence variants that are unique for the MRL mouse in the first intron of the p53-dependent transcript (in/dels) and in the vicinity of the p53-dependent promoter (single nucleotide substitutions). As we found no aberrant splicing variants, we quantified the levels of two p21 transcripts variants in various tissues of the MRL and the control B6 mouse. No dramatic decrease in the p21 transcript levels in the MRL mouse was revealed. The results indicate that the transcriptional regulation of p21 is not responsible for the reported deficit of p21 protein in the MRL mouse. The location of the MRL specific nucleotide sequence variants in the first intron of the p53-dependent p21 transcript and in the vicinity of the p53-dependent promoter may also be associated with the observation that the expression of p21 protein in the MRL mouse is not induced following γ-irradiation.

Cytuj jako

Pełna treść

pełna treść publikacji nie jest dostępna w portalu

Słowa kluczowe

Informacje szczegółowe

Kategoria:
Inne
Typ:
supllement, wydanie specjalne, dodatek
Opublikowano w:
Acta Biochimica Polonica nr 59, strony 90 - 90,
ISSN: 0001-527X
Tytuł wydania:
Acta Biochimica Polonica strony 90 - 90
Język:
angielski
Rok wydania:
2012
Opis bibliograficzny:
Górnikiewicz B., Sachadyn P.: Sequence variants of p21 gene of the MRL/MpJ mouse: a possible association with the deficit of p21 protein and regenerative phenotype.// Acta Biochimica Polonica. Supplement. -Vol. 59., nr. 3 (2012), s.90-90
Weryfikacja:
Politechnika Gdańska

wyświetlono 72 razy

Publikacje, które mogą cię zainteresować

Meta Tagi