The granzyme B gene is highly polymorphic in wild mice but essentially invariant in common inbred laboratory strains.
Tissue Antigens
; 70(3): 198-204, 2007 Sep.
Article
em En
| MEDLINE
| ID: mdl-17661907
ABSTRACT
Granzyme B is a 247 amino acid pro-apoptotic protease secreted by effector lymphocytes for the purpose of killing virus-infected cells. While the capacity of granzyme B to potently induce caspase-dependent apoptosis has long been recognized, it has only recently been found that human and mouse granzyme B activate overlapping but distinct apoptotic pathways. To investigate a possible evolutionary basis for this observation, we sequenced the exons and flanking intronic sequences of the mouse Gzmb gene from a variety of inbred laboratory strains and wild mice. The sequences of 12/13 inbred strains encoded identical proteins, the exception being DBA/2, whose sequence varied at two amino acids. By contrast with the laboratory strains, there was extensive polymorphism in the Gzmb gene of 54 wild mice and 28 wild-derived inbred mice examined, resulting in 2-18 amino acid differences in the predicted proteins, a discrepancy rate of up to 7.3%. Many of these amino acid variations were found in rat and/or human granzyme B. The granzyme B allotype of inbred laboratory strains could be identified in only one of three geographically dispersed clans of wild mice and was absent from all 28 wild-derived inbred strains. The Gzmb gene of Mus musculus castaneus, a close relative of laboratory mice, encoded six amino acid differences compared with the laboratory strains, all of which were also found in corresponding positions in the granzyme B molecules of wild mice. Unlike the protease, the extended granzyme B recognition and cleavage site in Bid, a key pro-apoptotic substrate, was invariant.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Variação Genética
/
Polimorfismo Conformacional de Fita Simples
/
Granzimas
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Tissue Antigens
Ano de publicação:
2007
Tipo de documento:
Article