Mouse Models of Neurodegenerative Diseases Laboratory (MMON)
Lead Research Organisation:
MRC Mammalian Genetics Unit
Abstract
Abstracts are not currently available in GtR for all funded research. This is normally because the abstract was not required at the time of proposal submission, but may be because it included sensitive information such as personal details.
Organisations
- MRC Mammalian Genetics Unit (Lead Research Organisation)
- University College London (Collaboration)
- University of Michigan (Collaboration)
- Hospital Universitario Insular de Gran Canaria (Collaboration)
- University of Padova (Collaboration)
- MRC Harwell (Collaboration)
- AbbVie Inc (Collaboration)
- Biodonostia (Collaboration)
- The Jackson Laboratory (Collaboration)
- Avantea (Collaboration)
- National Institutes of Health (NIH) (Collaboration)
- University of Leuven (Collaboration)
- UNIVERSITY OF SHEFFIELD (Collaboration)
- KING'S COLLEGE LONDON (Collaboration)
People |
ORCID iD |
Publications
Ali Z
(2023)
Mutation in the FUS nuclear localisation signal domain causes neurodevelopmental and systemic metabolic alterations.
in Disease models & mechanisms
Austin A
(2022)
Sectioning and Counting of Motor Neurons in the L3 to L6 Region of the Adult Mouse Spinal Cord.
in Current protocols
Birsa N
(2021)
FUS-ALS mutants alter FMRP phase separation equilibrium and impair protein translation.
in Science advances
Brown A
(2022)
TDP-43 loss and ALS-risk SNPs drive mis-splicing and depletion of UNC13A
in Nature
Cleverley K
(2021)
A novel knockout mouse for the small EDRK-rich factor 2 (Serf2) showing developmental and other deficits.
in Mammalian genome : official journal of the International Mammalian Genome Society
Cunningham TJ
(2020)
DNA Editing for Amyotrophic Lateral Sclerosis: Leading Off First Base.
in The CRISPR journal
De Giorgio F
(2019)
Transgenic and physiological mouse models give insights into different aspects of amyotrophic lateral sclerosis.
in Disease models & mechanisms
Devoy A
(2017)
Humanized mutant FUS drives progressive motor neuron degeneration without aggregation in 'FUSDelta14' knockin mice.
in Brain : a journal of neurology
| Description | Two PhD studentships from internal funding MRC Harwell |
| Amount | £120,000 (GBP) |
| Organisation | Medical Research Council (MRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 08/2019 |
| End | 08/2022 |
| Title | A new mouse model of motor neuron degeneration (FUS ALS) |
| Description | A new genetically engineered mouse model of FUS ALS |
| Type Of Material | Model of mechanisms or symptoms - mammalian in vivo |
| Year Produced | 2017 |
| Provided To Others? | Yes |
| Impact | Several labs now working with this model |
| Title | FUS mutant mice shed light on metabolic changes in disease |
| Description | Analysis of novel FUS mutant mice. |
| Type Of Material | Model of mechanisms or symptoms - mammalian in vivo |
| Year Produced | 2023 |
| Provided To Others? | Yes |
| Impact | of interest to ALS researchers |
| Title | New method using machine learning and microscopy to assess mouse neuromuscular junctions. |
| Description | Used machine learning to automate the detailed investigation of neuromuscular junctions in the mouse. Important for many mouse models of neurodegeneration. |
| Type Of Material | Improvements to research infrastructure |
| Year Produced | 2021 |
| Provided To Others? | Yes |
| Impact | Uptake by several users internationally. |
| Title | New mouse models including a new humanised TARDBP model |
| Description | New mouse models including a new humanised TARDBP model for neurodegeneration research including creating new mutations. |
| Type Of Material | Model of mechanisms or symptoms - mammalian in vivo |
| Year Produced | 2021 |
| Provided To Others? | Yes |
| Impact | Too soon |
| Title | Two new humanised FUS mutant strains P525L and Q519Ifs |
| Description | Fully humanised FUS gene, wildtype, onto which we have added the P525L mutation and, separately in a second strain of mouse, the Q519Ifs mutation, to try to more faithfully models human FUS motor neuron disease/amyotrophic lateral sclerosis. |
| Type Of Material | Model of mechanisms or symptoms - mammalian in vivo |
| Year Produced | 2019 |
| Provided To Others? | Yes |
| Impact | These mice have been presented at meetings, they are freely available, but we have not yet published on them. |
| Title | new humanised SOD1 mouse |
| Description | A new Humanised mouse model with the human SOD1 gene; this is a wildtype control for when we go forward to put in human amyotrophic lateral sclerosis mutations into SOD1. |
| Type Of Material | Model of mechanisms or symptoms - mammalian in vivo |
| Year Produced | 2019 |
| Provided To Others? | Yes |
| Impact | This mouse is freely available and has been presented at meetings, but we have not yet published on it. |
| Title | Engineered mouse FUS humanised ES cells. |
| Description | Mouse cell line that we may analyse rather than working with whole animals, thus helps with aims of NC3Rs. |
| Type Of Material | Data analysis technique |
| Provided To Others? | No |
| Impact | None yet. |
| Title | FUS homozygotes MEFs |
| Description | Working with a mouse model, an in vivo model, to produce IMMORTILISED cell lines so that we can drop our animal useage. |
| Type Of Material | Database/Collection of data |
| Year Produced | 2017 |
| Provided To Others? | Yes |
| Impact | Reduced mouse numbers |
| Description | Abraham Acevedo Arozena |
| Organisation | Hospital Universitario Insular de Gran Canaria |
| Department | La Fundación Canaria Instituto de Investigación Sanitaria de Canarias |
| Country | Spain |
| Sector | Public |
| PI Contribution | PhD student time and effort to develop a new mouse model |
| Collaborator Contribution | PhD supervision, DNA analysis, breeding and phenotypic analysis of a cohort of mice. |
| Impact | Posters at meetings |
| Start Year | 2016 |
| Description | Analysis of the FUS mouse translatome, Fratta, UCL |
| Organisation | University College London |
| Department | Marie Curie Palliative Care Research Department |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | contribution of the unique FUS Delta14 mouse model |
| Collaborator Contribution | RiboTagging and ChatCre breeding to pull down polysomes from the Delta14 mouse |
| Impact | Multidisiplinary output. No outcomes yet as just started. |
| Start Year | 2016 |
| Description | FUS humanised mice to U of Leuven |
| Organisation | University of Leuven |
| Country | Belgium |
| Sector | Academic/University |
| PI Contribution | The MMON lab and collaborators created humanised FUS mice, sent to a researcher into motor neuron disease in Leuven, and sent prepublication as part of our collaboration. |
| Collaborator Contribution | We created the mice for this collaboration, and carried out the initial characterisation. |
| Impact | Too soon. |
| Start Year | 2021 |
| Description | Greensmith lab small animal ephys |
| Organisation | University College London |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | We provide novel mouse models of neurological disorders |
| Collaborator Contribution | Analysis of nerve and muscle including by electrophysiology; all in mice. |
| Impact | Many papers include work from this collaboration. All papers are listed under the relevant grants. |
| Description | Humanised TARDBP mice to pharma |
| Organisation | AbbVie Inc |
| Department | AbbVie (UK) |
| Country | United Kingdom |
| Sector | Private |
| PI Contribution | We created the novel humanised TARDBP mice, with Abraham Acevedo from Spain. |
| Collaborator Contribution | The pharma company will use these mice to understand neurodegeneration. |
| Impact | Too soon. |
| Start Year | 2021 |
| Description | Labs at UCL for bespoke mouse models of neurodegeneration |
| Organisation | University College London |
| Department | Department of Neuroscience, Physiology and Pharmacology |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | Genome engineering expertise |
| Collaborator Contribution | In depth knowledge of specific forms of neurodegeneration Fratta, Isaacs, Greensmith, Schiavo, Wiseman. |
| Impact | None yet. |
| Start Year | 2017 |
| Description | MMON |
| Organisation | MRC Harwell |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | Collaboration with the Mouse Models of Neurodegeneration lab at MRC Harwell, analysis of homozygous and heterozygous mice |
| Collaborator Contribution | Breeding, inbreeding onto another background, and phenotypic analysis of homozygous and heterozygous mice. |
| Impact | Inbred mice on different backgrounds. Cohorts of mice of different ages, sex-matched with littermate controls, wildtype, heterozygous, homozygous, for phenotypic analysis. Analysis of different phenotypes ranging from behavioural through to physiological. |
| Start Year | 2017 |
| Description | Marc Ruepp, Sarah Mizielinksa, KCL -- Tom, repeat sequence cloning |
| Organisation | King's College London |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | Technology for cloning stably, expanded repeats. |
| Collaborator Contribution | Cell lines and disease expertise. |
| Impact | Pending |
| Start Year | 2020 |
| Description | Michael Ward, NIH - Tom repeat sequence cloning |
| Organisation | National Institutes of Health (NIH) |
| Country | United States |
| Sector | Public |
| PI Contribution | Repeat sequence cloning technique. |
| Collaborator Contribution | Cell lines and disease expertise. |
| Impact | pending. |
| Start Year | 2019 |
| Description | Michael Ward, NIH - Tom repeat sequence cloning |
| Organisation | National Institutes of Health (NIH) |
| Country | United States |
| Sector | Public |
| PI Contribution | Repeat sequence cloning technique. |
| Collaborator Contribution | Cell lines and disease expertise. |
| Impact | pending. |
| Start Year | 2019 |
| Description | Repeat sequence cloning, Peter Todd, U of Michigan |
| Organisation | University of Michigan |
| Country | United States |
| Sector | Academic/University |
| PI Contribution | Repeat sequence cloning technology to direct at Fragile X models. |
| Collaborator Contribution | Cell lines and disease expertise |
| Impact | pending |
| Start Year | 2020 |
| Description | Repeat sequencing cloning, pig, Avantea |
| Organisation | Avantea |
| Country | Italy |
| Sector | Public |
| PI Contribution | Technology for stably cloning repeat sequences |
| Collaborator Contribution | Animal models, cell lines. |
| Impact | Pending |
| Start Year | 2020 |
| Description | Tissues Jemeen Sreedharan |
| Organisation | King's College London |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | Tissues and data from mouse model of ALS |
| Collaborator Contribution | Comparison to existing model at KCL |
| Impact | pending |
| Start Year | 2020 |
| Description | Tom U of Sheffield for repeat cloning |
| Organisation | University of Sheffield |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | Tom Cunningham of MRC Harwell developed new cloning method for repeat expansion diseases. In use now in Sheffield, Matt Parker. |
| Collaborator Contribution | Cell lines and sequencing |
| Impact | Scientific research collaboration. No publications yet, too early. |
| Start Year | 2019 |
| Description | Tom with Bill Skarnes, Jax, for repeat cloning |
| Organisation | The Jackson Laboratory |
| Country | United States |
| Sector | Charity/Non Profit |
| PI Contribution | Tom Cunningham for repeat cloning protocol for expanded repeats. To be used by the Jackson laboratory in human cells. |
| Collaborator Contribution | Cell lines, technical expertise, outcome assays. |
| Impact | Laboratory research, publications pending. |
| Start Year | 2020 |
| Description | Tom with Bill Skarnes, Jax, for repeat cloning |
| Organisation | The Jackson Laboratory |
| Country | United States |
| Sector | Charity/Non Profit |
| PI Contribution | Tom Cunningham for repeat cloning protocol for expanded repeats. To be used by the Jackson laboratory in human cells. |
| Collaborator Contribution | Cell lines, technical expertise, outcome assays. |
| Impact | Laboratory research, publications pending. |
| Start Year | 2020 |
| Description | muscle in ALS models |
| Organisation | Biodonostia |
| Country | Spain |
| Sector | Public |
| PI Contribution | Tissues/mouse models of ALS |
| Collaborator Contribution | Expertise in muscle evalutaion |
| Impact | pending |
| Start Year | 2020 |
| Description | studying ribosomal proteins |
| Organisation | University of Padova |
| Department | Department of Neurosciences |
| Country | Italy |
| Sector | Hospitals |
| PI Contribution | Access to a unique mouse model of FUS ALS (Delta14) |
| Collaborator Contribution | Analysis of ribosomal proteins |
| Impact | No outputs yet |
| Start Year | 2017 |
| Description | with Pietro Fratta for ALS FUS/TDP43 mice |
| Organisation | University College London |
| Department | Institute of Neurology |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | creation of novel humanised mouse models of ALS |
| Collaborator Contribution | extensive analysis of transcriptomics and other measures. |
| Impact | Potentially novel approach to therapeutics for sporadic ALS. |
| Start Year | 2019 |
| Title | Antibody for FUS Delta 14 disease epitope. |
| Description | A disease specific antibody for our FUS Delta14 mouse model of motor neuron disease/amyotrophic lateral sclerosis. |
| IP Reference | |
| Protection | Protection not required |
| Year Protection Granted | 2017 |
| Licensed | Yes |
| Impact | Antibody for FUS Delta 14 sent out for academic use. |
| Description | DS special interest group |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | Local |
| Primary Audience | Professional Practitioners |
| Results and Impact | Wiseman F, LonDownS Consortium (2018) Understanding Down syndrome using Alzheimer's mouse models. Dementia in intellectual disabilities, Special Interest Group Meeting, London, London UK. Talk to mix of medical and other professionals working with peoplewith Down syndrome. |
| Year(s) Of Engagement Activity | 2018 |
| Description | Edgar talk to Parkinson's patients at Open Day |
| Form Of Engagement Activity | Participation in an open day or visit at my research institution |
| Part Of Official Scheme? | No |
| Geographic Reach | Regional |
| Primary Audience | Patients, carers and/or patient groups |
| Results and Impact | Open day at MRC Harwell; PI gave a talk to Parkinson's disease patients and carers. |
| Year(s) Of Engagement Activity | 2017 |
| Description | Interviewed on BBC Radio 4 for 'The Life Scientific' |
| Form Of Engagement Activity | A broadcast e.g. TV/radio/film/podcast (other than news/press) |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Public/other audiences |
| Results and Impact | Interviewed by Professor Jim Al-Khalili for a BBC Radio 4 broadcast on the 'Life Scientific'. |
| Year(s) Of Engagement Activity | 2019 |
| Description | Keynote at 2023 IMPC meeting Oxford, ALS models |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | INternational meeting of the International Mouse Phenotyping Consortium, 200 (?) attendees, presented our work and our field more broadly to the audience. |
| Year(s) Of Engagement Activity | 2023 |
| Description | Keynote presentation and Mouse Genetics Network meeting, York 2024 |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | Keynote talk and taking part in debate on use of mouse models and use of mouse models for neurodegenerative disease. |
| Year(s) Of Engagement Activity | 2024 |
| Description | Motor Neurone Disease/ALS Annual Symposium |
| Form Of Engagement Activity | A formal working group, expert panel or dialogue |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | Two posters presented at this annual meeting which has an international audience of scientists AND an audience of patients/carers/charity specialists. |
| Year(s) Of Engagement Activity | 2020 |
| Description | New Scientist Live 2018 MRC Harwell |
| Form Of Engagement Activity | A press release, press conference or response to a media enquiry/interview |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Public/other audiences |
| Results and Impact | New Scientist Live 2018, a public engagement activity for various disciplines in science, on 21 September 2018 |
| Year(s) Of Engagement Activity | 2018 |
| Description | Research seminar given at Inaugural ALS Symposium, Queen Square 2019, and in Umea, Sweden, and in Yeditepe University, Turkey 2019 |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | Three seminars given in UK, Turkey, Sweden, to specialist audiences of researchers, on the disease ALS. One outcome was collaboration and grant writing with the group of expert biochemists in Sweden. |
| Year(s) Of Engagement Activity | 2019 |
| Description | Translation in ALS short film (5 minutes) |
| Form Of Engagement Activity | A broadcast e.g. TV/radio/film/podcast (other than news/press) |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Public/other audiences |
| Results and Impact | We are currently making a short (5 minutes) film about Translation in ALS, for patients and carers and several of the specialist charities. The ALS charities will be able to use this film for raising hope and raising funding, and we will use it to try to gain funds for a longer film, from broadcasters. |
| Year(s) Of Engagement Activity | 2022,2023 |
| Description | UCL Postgraduate symposium poster |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | Local |
| Primary Audience | Postgraduate students |
| Results and Impact | De Giorgio A, Devoy A, Milioto C, Zhu F, MacKenzie K, Acevedo Arozena A, Fisher EMC (2018) Humanising the mouse Tardbp gene. UCL Sixth Annual Postgraduate Research Symposium, London, UK Poster presented to postgraduates outside field. |
| Year(s) Of Engagement Activity | 2018 |