OMIA:001504-9940 : Neuronal ceroid lipofuscinosis, 1 in Ovis aries (sheep)

In other species: dog

Categories: Lysosomal storage disease , Nervous system phene

Possibly relevant human trait(s) and/or gene(s)s (MIM numbers): 256730 (trait) , 600722 (gene)

Links to MONDO diseases:

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal recessive

Considered a defect: 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

By default, variants are sorted chronologically by year of publication, to provide a historical perspective. Readers can re-sort on any column by clicking on the column header. Click it again to sort in a descending order. To create a multiple-field sort, hold down Shift while clicking on the second, third etc relevant column headers.

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 Inferred EVA rsID Year Published PubMed ID(s) Acknowledgements
1353 Neuronal ceroid lipofuscinosis, 1 PPT1 delins, small (<=20) Genome-editing (CRISPR-Cas9) Oar_rambouillet_v1.0 1 g.15235231_15235231delinsTTA 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, 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, 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