OMIA:001504-9940 : Neuronal ceroid lipofuscinosis, 1 in Ovis aries (sheep) |
In other species: dog
Categories: Lysosomal storage disease , Nervous system phene
Links to possible relevant human trait(s) and/or gene(s) in OMIM: 256730 (trait) , 600722 (gene)
Links to relevant human diseases in MONDO:
Mendelian trait/disorder: yes
Mode of inheritance: Autosomal recessive
Disease-related: yes
Key variant known: yes
Year key variant first reported: 2019
Cross-species summary: One of several variants of neuronal ceroid lipofuscinosis (NCL) or Batten disease: CLN1; NCL1
Species-specific description: This disorder in sheep has been created by CRISPR/Cas9 gene editing. The affected sheep are, therefore, genetically-modified organisms (GMO).
History: Eaton et al. (2019) generated an ovine CLN1R151X model for human infantile neuronal ceroid lipofuscinosis using CRISPR/Cas9 technology. Nelvagal et al. (2022) "tested the efficacy of enzyme replacement therapy (ERT) by delivering monthly infusions of recombinant human PPT1 (rhPPT1) in PPT1-deficient mice (Cln1-/-), and CLN1R151X sheep ... . ... In CLN1R151X sheep, intracerebroventricular infusions resulted in widespread rhPPT1 distribution and positive treatment effects measured by quantitative structural magnetic resonance imaging and neuropathology."
Molecular basis: Eaton et al. (2019): "Three PPT1 homozygote sheep were generated by insertion of a disease-causing PPT1 (R151X) human mutation into the orthologous sheep locus".
Genetic engineering:
Yes - variants have been created artificially, e.g. by genetic engineering or gene editing
Have human generated variants been created, e.g. through genetic engineering and gene editing
Associated gene:
| Symbol | Description | Species | Chr | Location | OMIA gene details page | Other Links |
|---|---|---|---|---|---|---|
| PPT1 | palmitoyl-protein thioesterase 1 | Ovis aries | - | no genomic information (-..-) | PPT1 | Homologene, Ensembl , NCBI gene |
Variants
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WARNING! Inclusion of a variant in this table does not automatically mean that it should be used for DNA testing. Anyone contemplating the use of any of these variants for DNA testing should examine critically the relevant evidence (especially in breeds other than the breed in which the variant was first described). If it is decided to proceed, the location and orientation of the variant sequence should be checked very carefully.
Since October 2021, OMIA includes a semiautomated lift-over pipeline to facilitate updates of genomic positions to a recent reference genome position. These changes to genomic positions are not always reflected in the ‘acknowledgements’ or ‘verbal description’ fields in this table.
| OMIA Variant ID | Breed(s) | Variant Phenotype | Gene | Allele | Type of Variant | Source of Genetic Variant | Reference Sequence | Chr. | g. or m. | c. or n. | p. | Verbal Description | EVA ID | Year Published | PubMed ID(s) | Acknowledgements |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 1353 | Neuronal ceroid lipofuscinosis, 1 | PPT1 | delins, small (<=20) | Genome-editing (CRISPR-Cas9) | Oar_rambouillet_v1.0 | 1 | NC_040252.1:g.15235231_15235231delinsTTA | XP_004001885.2:p.(R151X) | 2019 | 31289301 |
Cite this entry
Nicholas, F. W., Tammen, I., & Sydney Informatics Hub. (2024). OMIA:001504-9940: Online Mendelian Inheritance in Animals (OMIA) [dataset]. https://omia.org/. https://doi.org/10.25910/2AMR-PV70
References
Note: the references are listed in reverse chronological order (from the most recent year to the earliest year), and alphabetically by first author within a year.
| 2022 | Eaton, S.L., Murdoch, F., Rzechorzek, N.M., Thompson, G., Hartley, C., Blacklock, B.T., Proudfoot, C., Lillico, S.G., Tennant, P., Ritchie, A., Nixon, J., Brennan, P.M., Guido, S., Mitchell, N.L., Palmer, D.N., Whitelaw, C.B.A., Cooper, J.D., Wishart, T.M. : |
| Modelling neurological diseases in large animals: Criteria for model selection and clinical assessment. Cells 11:2641, 2022. Pubmed reference: 36078049. DOI: 10.3390/cells11172641. | |
| Murray, S.J., Mitchell, N.L. : | |
| The translational benefits of sheep as large animal models of human neurological disorders. Front Vet Sci 9:831838, 2022. Pubmed reference: 35242840. DOI: 10.3389/fvets.2022.831838. | |
| Nelvagal, H.R., Eaton, S.L., Wang, S.H., Eultgen, E.M., Takahashi, K., Le, S.Q., Nesbitt, R., Dearborn, J.T., Siano, N., Puhl, A.C., Dickson, P.I., Thompson, G., Murdoch, F., Brennan, P.M., Gray, M., Greenhalgh, S.N., Tennant, P., Gregson, R., Clutton, E., Nixon, J., Proudfoot, C., Guido, S., Lillico, S.G., Whitelaw, C.B.A., Lu, J.Y., Hofmann, S.L., Ekins, S., Sands, M.S., Wishart, T.M., Cooper, J.D. : | |
| Cross-species efficacy of enzyme replacement therapy for CLN1 disease in mice and sheep. J Clin Invest 132:e163107, 2022. Pubmed reference: 36040802. DOI: 10.1172/JCI163107. | |
| 2019 | Eaton, S.L., Proudfoot, C., Lillico, S.G., Skehel, P., Kline, R.A., Hamer, K., Rzechorzek, N.M., Clutton, E., Gregson, R., King, T., O'Neill, C.A., Cooper, J.D., Thompson, G., Whitelaw, C.B., Wishart, T.M. : |
| CRISPR/Cas9 mediated generation of an ovine model for infantile neuronal ceroid lipofuscinosis (CLN1 disease). Sci Rep 9:9891, 2019. Pubmed reference: 31289301. DOI: 10.1038/s41598-019-45859-9. |
Edit History
- Created by Frank Nicholas on 23 Sep 2019
- Changed by Frank Nicholas on 23 Sep 2019
- Changed by Imke Tammen2 on 28 Sep 2021
- Changed by Imke Tammen2 on 11 Sep 2022
- Changed by Imke Tammen2 on 12 Dec 2023
- Changed by Imke Tammen2 on 18 Jan 2024