B6(Cg)-Fustm1.1Emcf/H

Status

Available to order

EMMA IDEM:11106
International strain nameB6(Cg)-Fustm1.1Emcf/H
Alternative nameFUS Delta14.
Strain typeTargeted Mutant Strains : Knock-in
Allele/Transgene symbolFustm1.1Emcf,
Gene/Transgene symbolFus

Information from provider

ProviderElizabeth Fisher
Provider affiliationNeurodegenerative Disease, University College London
Genetic informationTo create a mouse model that expresses mutant FUS (fused in sarcoma) at physiological levels, we targeted a human frameshift mutation (FUS p.G466VfsX14) into the mouse Fus locus. The frameshift arises from an A to G point mutation in the splice acceptor site of exon 14. This results in skipping of exon 14 during splicing and exon 15 (the last exon) being translated out of frame, creating a novel frame-shifted C-terminus. Thus we introduced the identical point mutation, g.13845 A to G (p.G459VfsX14) into the splice acceptor site of exon 14 of the endogenous mouse Fus locus. The human coding sequence of exon 15 was also knocked in to ensure the frameshift peptide sequence produced was identical to that of the human patient (14 residues long), because the mouse coding sequence lacks an early STOP codon and would produce a frameshift peptide that is 64 amino acids in length. The new strain was originally designated B6N;B6J-Fustm1Emcf/H, referred to here as FUS Delta14. FUS Delta14 mice were generated by homologous recombination in the C57BL/6N mouse embryonic stem cell (ESC) line JM8-F6, using standard procedures. Briefly, a construct of 8kb, introduced an A-to-G splice mutation at g.13845 and humanised the coding sequence of exon 15 through the following sequence changes: g.14230 C to T, g.14232 A to T, g.14234 C to G, g.14260 A to G and g.14266 ATTA insertion. Correct clones were initially identified through long-range PCR and copy number qPCR and validated by RT-PCR and Western blot for the truncated RNA/protein product, followed by DNA sequence verification. Mice were generated by injection of modified ESCs into B6(Cg)-Tyrc-2J/J (B6-albino) donor embryos, with the resultant chimeric male offspring crossed to B6-albino females to obtain germline transmission (GLT). GLT was confirmed by copy number qPCR. The FRT-flanked neo cassette was removed by crossing to the flpo recombinase-expression line B6(C3)-Tg(Pgk1-FLPo)10Sykr/J, which is maintained on the C57BL/6J background. The neo-negative line was backcrossed for a minimum of three generations onto the C57BL/6J background before experimental cohorts were bred.
Phenotypic informationHomozygous:
Late embryonic lethal in homozygotes on C57BL/6J background.

Heterozygous:
Progressive motor neuron loss in both sexes, but still only a mild phenotype by 18 months. Mild weight loss in males, in heterozygous animals.
References
  • Humanized mutant FUS drives progressive motor neuron degeneration without aggregation in 'FUSDelta14' knockin mice.;Devoy Anny, Kalmar Bernadett, Stewart Michelle, Park Heesoon, Burke Beverley, Noy Suzanna J, Redhead Yushi, Humphrey Jack, Lo Kitty, Jaeger Julian, Mejia Maza Alan, Sivakumar Prasanth, Bertolin Cinzia, Soraru Gianni, Plagnol Vincent, Greensmith Linda, Acevedo Arozena Abraham, Isaacs Adrian M, Davies Benjamin, Fratta Pietro, Fisher Elizabeth M C, ;2017;Brain : a journal of neurology;140;2797-2805; 29053787
Homozygous fertileno
Homozygous viableno
Homozygous matings requirednot known
Immunocompromisedno

Information from EMMA

Archiving centreMary Lyon Centre at MRC Harwell, Oxford, United Kingdom
Animals used for archivingheterozygous 0
Breeding at archiving centreThe mice have been maintained as het x wt matings on DBA/2JCrl background

Disease and phenotype information

MGI allele-associated human disease models

Orphanet associated rare diseases, based on orthologous gene matching

Literature references

  • Humanized mutant FUS drives progressive motor neuron degeneration without aggregation in 'FUSDelta14' knockin mice.;Devoy Anny, Kalmar Bernadett, Stewart Michelle, Park Heesoon, Burke Beverley, Noy Suzanna J, Redhead Yushi, Humphrey Jack, Lo Kitty, Jaeger Julian, Mejia Maza Alan, Sivakumar Prasanth, Bertolin Cinzia, Soraru Gianni, Plagnol Vincent, Greensmith Linda, Acevedo Arozena Abraham, Isaacs Adrian M, Davies Benjamin, Fratta Pietro, Fisher Elizabeth M C, ;2017;Brain : a journal of neurology;140;2797-2805; 29053787

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Availabilities

Requesting frozen sperm or embryos is generally advisable wherever possible, in order to minimise the shipment of live mice.

  • Frozen sperm. Delivered in 4 weeks (after paperwork in place). €1740*
  • Rederivation of mice from frozen stock, delivery time available upon request . €3880*
  • Tissue - Types of tissue, service fee and delivery time available upon request

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