TY - JOUR
T1 - Examining the homeostatic distribution of metals and Zn isotopes in Göttingen minipigs
AU - Mahan, Brandon
AU - Moynier, Frédéric
AU - Jørgensen, Arne Lund
AU - Habekost, Mette
AU - Siebert, Julien
PY - 2018/9/19
Y1 - 2018/9/19
N2 - The role of metals in biologic systems is manifold, and understanding
their behaviour in bodily processes, especially those relating to
neurodegenerative diseases, is at the forefront of medical science. The
function(s) of metals – such as the transition metals – and their
utility in both the diagnosis and treatment of diseases in human beings,
is often examined via the characterization of their
distribution in animal models, with porcine models considered
exceptional proxies for human physiology. To this end, we have
investigated the homeostatic distribution of numerous metals (Mg, K, Ca,
Mn, Fe, Cu, Zn, Rb and Mo), the non-metal P, and Zn isotopes in the
organs and blood (red blood cells, plasma) of Göttingen minipigs. These
results represent the first set of data outlining the homeostatic
distribution of metals and Zn isotopes in Göttingen minipigs, and
indicate a relatively homogeneous distribution of alkali/alkaline earth
metals and P among the organs, with generally lower levels in the blood,
while indicating more heterogeneous and systematic abundance patterns
for transition metals. In general, the distribution of all elements
analysed is similar to that found in humans. Our elemental abundance
data, together with data reported for humans in the literature, suggest
that element-to-element ratios, e.g. Cu/Mg, show potential as
simple diagnostics for diseases such as Alzheimer's. Isotopic data
indicate a heterogeneous distribution of Zn isotopes among the organs
and blood, with the liver, heart and brain being the most depleted in
heavy Zn isotopes, and the blood the most enriched, consistent with
observations in other animal models and humans. The Zn isotopic
composition of Göttingen minipigs displays a systematic offset towards
lighter δ66Zn values relative to mice and
sheep models, suggesting physiology that is more closely aligned with
that of humans. Cumulatively, these observations strongly suggest that
Göttingen minipigs are an excellent animal model for translational
research involving metals, and these data provide a strong foundation
for future research.
AB - The role of metals in biologic systems is manifold, and understanding
their behaviour in bodily processes, especially those relating to
neurodegenerative diseases, is at the forefront of medical science. The
function(s) of metals – such as the transition metals – and their
utility in both the diagnosis and treatment of diseases in human beings,
is often examined via the characterization of their
distribution in animal models, with porcine models considered
exceptional proxies for human physiology. To this end, we have
investigated the homeostatic distribution of numerous metals (Mg, K, Ca,
Mn, Fe, Cu, Zn, Rb and Mo), the non-metal P, and Zn isotopes in the
organs and blood (red blood cells, plasma) of Göttingen minipigs. These
results represent the first set of data outlining the homeostatic
distribution of metals and Zn isotopes in Göttingen minipigs, and
indicate a relatively homogeneous distribution of alkali/alkaline earth
metals and P among the organs, with generally lower levels in the blood,
while indicating more heterogeneous and systematic abundance patterns
for transition metals. In general, the distribution of all elements
analysed is similar to that found in humans. Our elemental abundance
data, together with data reported for humans in the literature, suggest
that element-to-element ratios, e.g. Cu/Mg, show potential as
simple diagnostics for diseases such as Alzheimer's. Isotopic data
indicate a heterogeneous distribution of Zn isotopes among the organs
and blood, with the liver, heart and brain being the most depleted in
heavy Zn isotopes, and the blood the most enriched, consistent with
observations in other animal models and humans. The Zn isotopic
composition of Göttingen minipigs displays a systematic offset towards
lighter δ66Zn values relative to mice and
sheep models, suggesting physiology that is more closely aligned with
that of humans. Cumulatively, these observations strongly suggest that
Göttingen minipigs are an excellent animal model for translational
research involving metals, and these data provide a strong foundation
for future research.
UR - http://www.scopus.com/inward/record.url?scp=85053861200&partnerID=8YFLogxK
U2 - 10.1039/c8mt00179k
DO - 10.1039/c8mt00179k
M3 - Article
C2 - 30128473
SN - 1756-5901
VL - 10
SP - 1264
EP - 1281
JO - Metallomics
JF - Metallomics
IS - 9
ER -