IMPC phenotypes (gene matching)
B6N;Cg-Fusem2(FUS*Q519I)Emcf/H
| Status | Available to order |
| EMMA ID | EM:16089 |
| Citation information | RRID:IMSR_EM:16089 Research Resource Identifiers (RRID) are persistent unique ID numbers assigned to help researchers cite key resources (e.g. antibodies, model organisms and software projects) in the biomedical literature to improve transparency and reproducibility in research. See https://www.rrids.org/ for more information. |
| International strain name | B6N;Cg-Fusem2(FUS*Q519I)Emcf/H |
| Alternative name | B6N;Cg-Fusem2(FUS*Q519I)Emcf/H |
| Strain type | Endonuclease-mediated |
| Allele/Transgene symbol | Fus |
| Gene/Transgene symbol | Fus |
Information from provider
| Provider | Elizabeth Fisher |
| Provider affiliation | Neuromuscular Diseases, UCL Queen Square Institute of Neurology |
| Additional owner | This strain is co-owned by UCL and MRC Harwell |
| Genetic information | Het for Humanised FUS carrying Q519IFS frameshift: 1 copy of Humanised FUS carrying Q519IFS frameshift 1 copy of murine WT Fus. The frameshift was generated by CRISPR edit of an existing BAC insertion to carry the Q519IFS change, and an additional silent change to prevent re-processing of the engineered allele. The BAC construct (BAC RP24-297F14), engineered to harbor the human FUS genomic sequence flanked by large regions of mouse homology, was used as a donor to replace endogenous mouse Fus with human FUS in mouse ES cells via homologous recombination. This construct was electroporated into the 129/SvJ mouse embryonic stem cell (ESC) line R1, humanising Fus in the mouse genome. Correctly targeted clones were initially identified through Loss-Of-Allele (LOA) copy number qPCR and validated by RT-PCR and western blot for the humanised RNA/protein product. Mice were generated by injection of modified ESCs into C57BL/6Brd-Tyrc-Brd/Wtsi donor blastocysts, with the resultant chimeric male offspring crossed to C57BL/6J females to obtain germline transmission (GLT). Following confirmation of GLT, hFUS heterozygous mice were bred one further generation to the C57BL/6J strain, followed by crossing to the Gt(ROSA)26Sortm2(CAG-flpo,-EYFP)Ics line (C57BL/6Ntac background) to excise the FRT-flanked Neo selection cassette. The Neo-negative line was then backcrossed for at least six further generations onto the C57BL6/J background before experimental cohorts were bred. Genotyping was performed by LOA copy number qPCR using the commercially available probesets Mm00217486_cn, Mm00217500_cn, Hs02670898_cn, Hs05441121_cn (Life Technologies). The point mutation was generated by CRISPR editing of the existing BAC insertion to carry the P525L change, and an additional silent change to prevent re-processing of the engineered allele. The point mutation was generated by retargeting the strain B6J.Cg-Fustm3.1(FUS)Emcf/H (EM:13073) and has also been archived on a C3H/HeH and 129 background. |
| Phenotypic information | Mice display a high prevalence of Malocclusion and poor viability. The point mutation was mainly studied and characterised on a C3H/HeH background. |
| Breeding history | These mice were derived from the parental humanised FUS line HU-FUS-WT-B6 which was made in 129 ES cells and crossed to B6J. Backcrossed to C57BL/6NTac for at least 4 generations. |
| References | None available |
| Homozygous fertile | not known |
| Homozygous viable | not known |
| Homozygous matings required | no |
| Immunocompromised | no |
Information from EMMA
| Archiving centre | Mary Lyon Centre at MRC Harwell, Oxford, United Kingdom |
Disease and phenotype information
Orphanet associated rare diseases, based on orthologous gene matching
- Amyotrophic lateral sclerosis / Orphanet_803
- Juvenile amyotrophic lateral sclerosis / Orphanet_300605
MGI phenotypes (gene matching)
- small thymus / MGI
- motor neuron degeneration / MGI
- decreased motor neuron number / MGI
- abnormal neuromuscular synapse morphology / MGI
- small testis / MGI
- decreased body weight / MGI
- decreased body size / MGI
- abnormal gait / MGI
- abnormal suckling behavior / MGI
- impaired limb coordination / MGI
- increased mortality induced by gamma-irradiation / MGI
- postnatal growth retardation / MGI
- reduced female fertility / MGI
- male infertility / MGI
- decreased litter size / MGI
- premature death / MGI
- no abnormal phenotype detected / MGI
- lymphoid hypoplasia / MGI
- abnormal immunoglobulin level / MGI
- no phenotypic analysis / MGI
- abnormal chromosome morphology / MGI
- aneuploidy / MGI
- chromosome breakage / MGI
- decreased lymphocyte cell number / MGI
- decreased B cell number / MGI
- abnormal male meiosis / MGI
- abnormal hippocampus pyramidal cell morphology / MGI
- postnatal lethality, incomplete penetrance / MGI
- neonatal lethality, complete penetrance / MGI