PNAS: Animal models reveal GPI anchoring defects

January 12, 2021 /----- Mental impairment, movement disorders and stunting are typical manifestations of rare diseases caused by GPI protein defects.
at the University of Bonn and the Max Planck Institute for Molecular Genetics used genetic engineering to create a mouse that mimics these patients well.
in this animal model, genetic mutations can impair the transmission of stimuli in brain synapses in GPI anchor protein defects.
results are now published in the journal PNAS.
(Photo Source: Www.pixabay.com) Just as ships anchor to the bottom of the ocean in storms and waves, GPI anchoring (GPI -glycophosphatidol) ensures that special proteins remain outside living cells.
if the GPI anchor does not function properly due to a genetic mutation, it can disrupt signaling and transport between cells.
Peter Krawitz, of the Institute of Genomic Statistics and Bioinsynthetics at the University Hospital of Bonn, explains: "GPI anchor defects include a group of rare diseases that mainly cause mental retardation and stunting."
mutations in the PIGV gene have been found in most European patients.
it encodes an enzyme that is essential for GPI anchor synthesis.
researchers at the Max-Pranck Institute for Molecular Genetics and colleagues used CRISPR-Cas9 gene editing techniques to modify the PIGV gene in mice based on patient models.
of behavioral tests have shown that this mouse model is very close to reflecting diseases observed in humans," said Miguel Rodriguez de los Santos of the Institute of Medical Genetics and Human Genetics, a charity.
" conducted behavioral tests on genetically modified mice in collaboration with scientists at the Animal Outcomes Core Facility, a cluster of excellence at NeuroCure in Chaité.
like patients, animals exhibit cognitive impairment.
were significantly less spatially desirable and had a change in social behavior than mice without the mutation.
that patients with GPI anchoring defects also exhibit this sociality in some cases.
mice that changed pigV also showed deviations in circadian rhythms.
researchers know from preliminary studies that the sea masse played a major role in GPI anchoring defects.
brain structure is similar to the shape of the sea horse and can access memories.
researchers studied small glial cells and sub-neurons in genetically modified mice.
glial cells are brain immune cells that resist intruders.
neurons are also responsible for memory retrieval.
of these two cell types have been mismodulation," said Rodriguez de los Santos, a research editor at the center of the study.
" this may explain why mice showed directional discernment defects in the tests.
(Bioon.com) Source: Researchers create an animal model for study GPI anchories Original source: Miguel Rodriguez de los Santos et al, A CRISPR-Cas9-engineered mouse model for GPI-anchored financial mirrors human phenotypes and exhibits hippocampal synaptic dysfunctions, Proceedings of the National Academy of Sciences (2021). DOI: 10.1073/pnas.2014481118