Mid-Gestation lethality of Atxn2l-Ablated Mice.

International Journal of Molecular Sciences
Jana KeySuzana Gispert

Abstract

Depletion of yeast/fly Ataxin-2 rescues TDP-43 overexpression toxicity. In mouse models of Amyotrophic Lateral Sclerosis via TDP-43 overexpression, depletion of its ortholog ATXN2 mitigated motor neuron degeneration and extended lifespan from 25 days to >300 days. There is another ortholog in mammals, named ATXN2L (Ataxin-2-like), which is almost uncharacterized but also functions in RNA surveillance at stress granules. We generated mice with Crispr/Cas9-mediated deletion of Atxn2l exons 5-8, studying homozygotes prenatally and heterozygotes during aging. Our novel findings indicate that ATXN2L absence triggers mid-gestational embryonic lethality, affecting female animals more strongly. Weight and development stages of homozygous mutants were reduced. Placenta phenotypes were not apparent, but brain histology showed lamination defects and apoptosis. Aged heterozygotes showed no locomotor deficits or weight loss over 12 months. Null mutants in vivo displayed compensatory efforts to maximize Atxn2l expression, which were prevented upon nutrient abundance in vitro. Mouse embryonal fibroblast cells revealed more multinucleated giant cells upon ATXN2L deficiency. In addition, in human neural cells, transcript levels of ATXN2L were i...Continue Reading

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Citations

Sep 17, 2020·International Journal of Molecular Sciences·Aleksandar ArsovićGeorg Auburger
Dec 8, 2020·American Journal of Medical Genetics. Part a·Fatema AlzahraniFowzan S Alkuraya

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Methods Mentioned

BETA
antisense-oligonucleotides
affinity
nucleotide exchange
dissection
FCS
biopsies
genotyping
PCR
Assay

Software Mentioned

Image Studio Lite
Coexpedia
RegRNA2
GraphPad Prism
STRING

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