Granulin Knock Out Zebrafish Lack Frontotemporal Lobar Degeneration and Neuronal Ceroid Lipofuscinosis Pathology
- Solchenberger, B., Russell, C., Kremmer, E., Haass, C., Schmid, B.
- PLoS One 10: e0118956 (Journal)
- Registered Authors
- Haass, Christian, Russell, Claire, Schmid, Bettina, Solchenberger, Barbara
- MeSH Terms
- Base Sequence
- Frontotemporal Lobar Degeneration/genetics*
- Gene Knockout Techniques*
- Intercellular Signaling Peptides and Proteins/deficiency*
- Intercellular Signaling Peptides and Proteins/genetics*
- Molecular Sequence Data
- Motor Neurons/cytology
- Neuronal Ceroid-Lipofuscinoses/genetics*
- Spinal Cord/cytology
- Zebrafish Proteins/deficiency
- Zebrafish Proteins/genetics
- 25785851 Full text @ PLoS One
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.
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.