Genetic Mutant Models
Previous research on mutant mouse models
focused on the effects of mutations in key DNA repair pathways
to the metabolome, in urine and blood. Parp1-/- mice
are deficient in base excision repair, ATM-/- in double
strand break repair and radiation signaling, and Prkdc-/-
(Scid) deficient in non-homologous end joining. While Parp1-/-
show delayed responses and a general equal number of metabolites
of high and low levels of metabolites between irradiated wild
type and mutant, Scid mice are characterized by an overall decreased
level of metabolites, whereas Atm mice by high levels of excretion.
New research will focus on pro- and anti-inflammatory mouse models
to identify the contribution of immune responses and signaling
in the metabolic signature.
Delayed response of small molecule excretion in
Laiakis EC, Pannkuk EL, Diaz-Rubio ME, Wang YW,
Mak TD, Simbulan-Rosenthal CM, Brenner DJ, Fornace AJ.
Implications of genotypic differences in the generation of a urinary
metabolomics radiation signature. Mutat Res