Modification: C9orf72: Knock-Out
Disease Relevance: Frontotemporal Dementia, Amyotrophic Lateral Sclerosis
Strain Name: 3110043O21Riktm1(KOMP)Mbp
Genetic Background: C57BL/6N
Availability: Available through the UC Davis Knockout Mouse Project (KOMP) Repository, gene 3110043021Rik; Cryopreserved
These mice have a targeted deletion of 3110043O21Rik, the murine homologue of human C9ORF72. No C9ORF72 gene product (mRNA or protein) is detected in homozygous null animals (O’Rourke et al., 2016). Homozygous null animals are viable, normal in size, and have a normal life span. They show no signs of motor neuron disease up to 17 months of age. Close examination reveals that homozygous null animals have enlarged spleens and lymph nodes. Macrophages and microglia show evidence of defective endosomal trafficking and increased expression of inflammatory markers such as IL-1β, IL-6, IL-10. Behaviorally, homozygous C9orf72 knockouts exhibit decreased exploration in the open-field test. Phenotypes of hemizygous animals are largely similar to wildtype controls. No phenotypic differences were observed between male and female mice, when examined.
The mouse 3110043O21Rik gene (homologue of human C9ORF72) was inactivated by deleting a region containing exons 2-6, which includes the start codon. The targeting vector contained expression cassettes, flanked by FRT sites, for lacZ and neo as selectable markers.
When visualized, these models will distributed over a 18 month timeline demarcated at the following intervals: 1mo, 3mo, 6mo, 9mo, 12mo, 15mo, 18mo+.
- Cortical Neuron Loss
- Lower Motor Neuron Loss
- Cytoplasmic Inclusions
- NMJ Abnormalities
- Muscle Atrophy
- Body Weight
- Premature Death
Cortical Neuron Loss
Lower Motor Neuron Loss
Reduced activity on open-field test. No abnormalities in grip strength or Rotarod performance.
Last Updated: 03 Jun 2016
- O'Rourke JG, Bogdanik L, Yáñez A, Lall D, Wolf AJ, Muhammad AK, Ho R, Carmona S, Vit JP, Zarrow J, Kim KJ, Bell S, Harms MB, Miller TM, Dangler CA, Underhill DM, Goodridge HS, Lutz CM, Baloh RH. C9orf72 is required for proper macrophage and microglial function in mice. Science. 2016 Mar 18;351(6279):1324-9. PubMed.