Granulin knock out zebrafish lack frontotemporal lobar degeneration and neuronal ceroid lipofuscinosis pathology

PloS One
Barbara SolchenbergerBettina Schmid

Abstract

Loss of function mutations in granulin (GRN) are linked to two distinct neurological disorders, frontotemporal lobar degeneration (FTLD) and neuronal ceroid lipofuscinosis (NCL). It is so far unknown how a complete loss of GRN in NCL and partial loss of GRN in FTLD can result in such distinct diseases. In zebrafish, there are two GRN homologues, Granulin A (Grna) and Granulin B (Grnb). We have generated stable Grna and Grnb loss of function zebrafish mutants by zinc finger nuclease mediated genome editing. Surprisingly, the grna and grnb single and double mutants display neither spinal motor neuron axonopathies nor a reduced number of myogenic progenitor cells as previously reported for Grna and Grnb knock down embryos. Additionally, grna-/-;grnb-/- double mutants have no obvious FTLD- and NCL-related biochemical and neuropathological phenotypes. Taken together, the Grna and Grnb single and double knock out zebrafish lack any obvious morphological, pathological and biochemical phenotypes. Loss of zebrafish Grna and Grnb might therefore either be fully compensated or only become symptomatic upon additional challenge.

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Citations

Oct 21, 2017·Brain : a Journal of Neurology·Babykumari P ChitramuthuAndrew Bateman
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Oct 8, 2020·Brain Research Bulletin·Konstantin N ZabegalovAllan V Kalueff

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Methods Mentioned

BETA
biopsies
confocal microscopy
transgenic
PCR
ELISA

Key Resources (RRID) Mentioned

AB_477583
AB_2069021
AB_528428
AB_531910
AB_430834
AB_430833
AB_10566289

Software Mentioned

mTrackJ
CompoZr
ZebraBox Revolution
ImageJ
Graph Pad Prism
Tardbp
ZebraLab

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