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PLoS One. 2015 Mar 18;10(3):e0118956. doi: 10.1371/journal.pone.0118956. eCollection 2015.

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

Author information

1
Adolf-Butenandt-Institute-Biochemistry, Ludwig-Maximilians University Munich, Munich, Germany.
2
Department of Comparative Biomedical Sciences, Royal Veterinary College, London, United Kingdom.
3
Institute of Molecular Immunology, Helmholtz Center Munich, Munich, Germany.
4
Adolf-Butenandt-Institute-Biochemistry, Ludwig-Maximilians University Munich, Munich, Germany; Munich Cluster for Systems Neurology (SyNergy), Munich, Germany; German Center for Neurodegenerative Diseases (DZNE) Munich, Munich, Germany.

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.

PMID:
25785851
PMCID:
PMC4365039
DOI:
10.1371/journal.pone.0118956
[Indexed for MEDLINE]
Free PMC Article

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