PUBLICATION

Granulin Knock Out Zebrafish Lack Frontotemporal Lobar Degeneration and Neuronal Ceroid Lipofuscinosis Pathology

Authors
Solchenberger, B., Russell, C., Kremmer, E., Haass, C., Schmid, B.
ID
ZDB-PUB-150319-2
Date
2015
Source
PLoS One   10: e0118956 (Journal)
Registered Authors
Haass, Christian, Russell, Claire, Schmid, Bettina, Solchenberger, Barbara
Keywords
none
MeSH Terms
  • Intercellular Signaling Peptides and Proteins/deficiency*
  • Intercellular Signaling Peptides and Proteins/genetics*
  • Gene Knockout Techniques*
  • Frontotemporal Lobar Degeneration/genetics*
  • Animals
  • Base Sequence
  • Female
  • Phenotype
  • Zebrafish*
  • Neuronal Ceroid-Lipofuscinoses/genetics*
  • Mutation
  • Zebrafish Proteins/deficiency
  • Zebrafish Proteins/genetics
  • Male
  • Humans
  • Molecular Sequence Data
  • Spinal Cord/cytology
  • Motor Neurons/cytology
(all 18)
PubMed
25785851 Full text @ PLoS One
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.
Genes / Markers
Figures
Figure Gallery (4 images)
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Expression
No data available
Phenotype
No data available
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
mde33
    		Small Deletion
    mde54a
      		Small Deletion
      mde54b
        		Small Deletion
        mde54c
          		Indel
          mde357a
            		Small Deletion
            mde360
              		Indel
              mde369
                		Insertion
                zf147TgTransgenic Insertion
                  1 - 8 of 8
                  Show
                  Human Disease / Model
                  Human Disease Fish Conditions Evidence
                  frontotemporal dementiaTAS
                  neuronal ceroid lipofuscinosisTAS
                  1 - 2 of 2
                  Show
                  Sequence Targeting Reagents
                  No data available
                  Fish
                  Fish
                  grnamde33/mde33
                  grnamde54a/mde54a
                  grnamde54b/mde54b
                  grnamde54c/mde54c
                  grnbmde357a/mde357a
                  grnbmde360/mde360
                  grnbmde369/mde369
                  zf147Tg
                  1 - 8 of 8
                  Show
                  Antibodies
                  Orthology
                  No data available
                  Engineered Foreign Genes
                  Marker Marker Type Name
                  EGFPEFGEGFP
                  1 - 1 of 1
                  Show
                  Mapping
                  No data available
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                  Citation
                  Solchenberger, B., Russell, C., Kremmer, E., Haass, C., Schmid, B. (2015) Granulin Knock Out Zebrafish Lack Frontotemporal Lobar Degeneration and Neuronal Ceroid Lipofuscinosis Pathology. PLoS One. 10:e0118956.