SLC30A3-deficient male mice were found to exhibit autistic behaviors, increased cortical volume and neurite density, and elevated BNDF levels and MMP-9 activity; treatment with the MMP inhibitor minocycline attenuated BDNF levels, megalencephaly and autistic behaviors (Yoo et al., 2016). SLC30A3-null mice had previously been shown to display increased sensitivity to hyperthermia-induced seizures that model febrile seizures (Hildebrand et al., 2015).
Molecular Function
This gene encodes a synaptic zinc transporter that is involved in the accumulation of zinc in synaptic vesicles.
External Links
References
Type
Title
Type of Disorder
Associated Disorders
Author, Year
Primary
Autism phenotypes in ZnT3 null mice: Involvement of zinc dyshomeostasis, MMP-9 activation and BDNF upregulation.
Model Type:
Genetic
Model Genotype:
Homozygous
Mutation:
Slc30a3 KO ( null) mice with deletion of exons 1-4
Allele Type: Knockout
Strain of Origin: 129Sv/Ev
Genetic Background: C57Bl/129Sv
ES Cell Line: Unreported
Mutant ES Cell Line: AB1 cells
Model Source: Richard D. Palmiter, University of Washington (PMID 21245308)
Description: Male slc30a3 null mice showed reduced total distance of travel compared to male wt mice
Exp Paradigm: Measured total distance travelled, males only
Description: Male slc30a3 null mice have more neurons in the frontal cortex than wt male mice
Exp Paradigm: Neun, smi32 immunohistochemistry: frontal cortex; neun, smi32 western blot: frontal cortex
Description: Male slc30a3 null mice have a larger frontal cerebral cortex of the brain than wt male mice
Exp Paradigm: Magnetic resonance imaging (mri)
Description: Slc30a3 null mice had higher levels of trkb in the cortex and hippocampus compared to wt mice, levels of receptors nt4/5, ngf, and p75ntr were not altered in the cortex
Exp Paradigm: Immunohistochemistry: cortex; western blot: cortex-immunohistochemistry: cortex and hippocampus
Description: Slc30a3 null mice had greater neurite density than in wt mice
Exp Paradigm: Smi32 (neurofilament h non-phosphorylated) immunostaining, males only
Description: Slc30a3 null mice had higher levels of trkb in the cortex and hippocampus compared to wt mice, levels of receptors nt4/5, ngf, and p75ntr were not altered in the cortex
Exp Paradigm: Immunohistochemistry: cortex; western blot: cortex- western blot: cortex and hippocampus
Description: Male slc30a3 null mice have overall increased levels of bdnf than wt male mice, male slc30a3 mice have higher levels of precurosor and mature form of bdnf in the cerebral cortex compared to wt mice, male slc30a3 mice have higher levels of the mature form of bdnf in the hippocampus compared to wt mice
Exp Paradigm: Immunohistochemistry: total bdnf;
Description: Male slc30a3 null mice showed increased marble burying compared to male wt mice
Exp Paradigm: The number of marbles over half buried in the bedding material in 10 minutes was recorded
Description: Male slc30a3 null mice spent more time in the empty chamber and less time in the chamber containing stranger 1 compared to male wt mice
Exp Paradigm: Time spent in the empty chamber vs time spent in the chamber containing a stranger mouse in a wire cage, measured
Description: Male slc30a3 null mice show self-grooming at an over 2 fold higher level than wt male mice
Exp Paradigm: Three-chamber social approach test; general observations
Description: Male slc30a3 null mice interact more with the now familiar stranger 1 than with stranger 2 compared to male wt mice
Exp Paradigm: Time spent interacting with familiar mouse vs novel stimulus mouse was measured
Description: Male slc30a3 null mice showed less total interaction time compared to male wt mice
Exp Paradigm: A single mouse was allowed to freely explore a new environment for 10 minutes and an unfamiliar same strain and age male or female mouse was introduced to the cage and allowed to explore it freely for 10 minutes as a test session
Description: Metallothioneins 1 and 2 known to be induced by increases in cytosolic free zinc levels, substantially increase in slc30a3 null brains compared to wt brains
Exp Paradigm: Metallothioneins 1 and 2 immunostaining
Description: Shank3 expression, modulated by incracellular zinc levels, increased in slc30a3 null mice cortices compared to wt mice cortices
Exp Paradigm: Total rna was extracted from astrocytes using trizol reagent
Description: Male slc30a3 null mice have increased levels of mmp9 in the cerebral cortex and corpus callossum compared to wt mice
Exp Paradigm: Enz-chek gelatinase assay kit was used for in situ zymography-immunohistochemistry: neuronal
Description: Male slc30a3 null mice have increased levels of mmp9 in the cerebral cortex and corpus callossum compared to wt mice
Exp Paradigm: Enz-chek gelatinase assay kit was used for in situ zymography- western blot: cortex and corpus callossum
