TY - JOUR
T1 - Re-partitioning of Cu and Zn isotopes by modified protein
expression
AU - Büchl, A
AU - Hawkesworth, C
AU - Ragnarsdottir, K V
AU - Brown, David R
PY - 2008/10/10
Y1 - 2008/10/10
N2 - Cu and Zn have naturally occurring non radioactive isotopes, and their isotopic systematics in a
biological context are poorly understood. In this study we used double focussing mass
spectroscopy to determine the ratios for these isotopes for the first time in mouse brain. The Cu
and Zn isotope ratios for four strains of wild-type mice showed no significant difference (δ65Cu -
0.12 to -0.78 permil; δ66Zn -0.23 to -0.48 permil). We also looked at how altering the expression
of a single copper binding protein, the prion protein (PrP), alters the isotope ratios. Both knockout
and overexpression of PrP had no significant effect on the ratio of Cu isotopes. Mice brains
expressing mutant PrP lacking the known metal binding domain have δ65Cu isotope values of on
average 0.57 permil higher than wild-type mouse brains. This implies that loss of the copper binding
domain of PrP increases the level of 65Cu in the brain. δ66Zn isotope values of the transgenic mouse
brains are enriched for 66Zn to the wild-type mouse brains. Here we show for the first time that
the expression of a single protein can alter the partitioning of metal isotopes in mouse brains. The
results imply that the expression of the prion protein can alter cellular Cu isotope content.
AB - Cu and Zn have naturally occurring non radioactive isotopes, and their isotopic systematics in a
biological context are poorly understood. In this study we used double focussing mass
spectroscopy to determine the ratios for these isotopes for the first time in mouse brain. The Cu
and Zn isotope ratios for four strains of wild-type mice showed no significant difference (δ65Cu -
0.12 to -0.78 permil; δ66Zn -0.23 to -0.48 permil). We also looked at how altering the expression
of a single copper binding protein, the prion protein (PrP), alters the isotope ratios. Both knockout
and overexpression of PrP had no significant effect on the ratio of Cu isotopes. Mice brains
expressing mutant PrP lacking the known metal binding domain have δ65Cu isotope values of on
average 0.57 permil higher than wild-type mouse brains. This implies that loss of the copper binding
domain of PrP increases the level of 65Cu in the brain. δ66Zn isotope values of the transgenic mouse
brains are enriched for 66Zn to the wild-type mouse brains. Here we show for the first time that
the expression of a single protein can alter the partitioning of metal isotopes in mouse brains. The
results imply that the expression of the prion protein can alter cellular Cu isotope content.
UR - http://www.scopus.com/inward/record.url?scp=54349124851&partnerID=8YFLogxK
UR - http://dx.doi.org/10.1186/1467-4866-9-11
U2 - 10.1186/1467-4866-9-11
DO - 10.1186/1467-4866-9-11
M3 - Article
VL - 9
JO - Geochemical Transactions
JF - Geochemical Transactions
IS - 11
ER -