OMIA:001443-9940 : Neuronal ceroid lipofuscinosis, 6 in Ovis aries (sheep) |
In other species: dog , domestic cat
Categories: Lysosomal storage disease , Nervous system phene
Links to possible relevant human trait(s) and/or gene(s) in OMIM: 601780 (trait) , 606725 (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: 2006
Cross-species summary: One of several variants of neuronal ceroid lipofuscinosis (NCL) or Batten disease: CLN6; NCL6
Species-specific name: Battens disease
Species-specific symbol: NCL
History: This disorder in sheep was first reported by Jolly and West (1976) and Jolly et al. (1980). Its classification as NCL6 was first reported by Broom et al. (1998).
Mapping: Homozygosity mapping of the Merino disorder enabled Cook et al. (2002) to locate this disorder on chromosome OAR7q13-15. Linkage analysis strongly implicated the CLN6 gene as causing NCL in South Hampshire sheep (Broom et al., 2001), and precluded the CLN6 gene as being related to CLN in the Borderdale breed (Tammen et al., 2006).
Molecular basis: Using the comparative positional candidate gene approach, Tammen et al. (2006) discovered a missense mutation (c.184C>T; p.Arg62Cys)in the CLN6 gene, responsible for NCL6 in Merino sheep. Mohd Ismail et al. (2012) reported the causal mutation in the South Hampshire breed as a deletion of exon 1 of the CLN6 gene.
Breeds:
Merino (Sheep) (VBO_0001508),
South Hampshire, New Zealand (Sheep) (VBO_0016317).
Breeds in which the phene has been documented. (If a likely causal variant has been documented for the phene, see the variant table breeds in which the variant has been reported).
Associated gene:
| Symbol | Description | Species | Chr | Location | OMIA gene details page | Other Links |
|---|---|---|---|---|---|---|
| CLN6 | ceroid-lipofuscinosis, neuronal 6, late infantile, variant | Ovis aries | 7 | NC_056060.1 (15028256..15012915) | CLN6 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 671 | South Hampshire, New Zealand (Sheep) | Neuronal ceroid lipofuscinosis | CLN6 | deletion, gross (>20) | Naturally occurring variant | Oar_rambouillet_v1.0 | 7 | deletion of exon 1 | 2013 | 23338040 | ||||||
| 234 | Merino (Sheep) | Neuronal ceroid lipofuscinosis, 6 | CLN6 | missense | Naturally occurring variant | Oar_rambouillet_v1.0 | 7 | NC_040258.1:g.16039510G>A | NM_001040289.1:c.184C>T | NP_001035379.1:p.(R62C) | protein and cDNA position based on NP_001035379.1 and NM_001040289.1, respectively | rs399747319 | 2006 | 17046213 | The genomic location on Oar_rambouillet_v1.0 was determined by Katie Eager, EMAI, NSW Department of Primary Industries. |
Cite this entry
Nicholas, F. W., Tammen, I., & Sydney Informatics Hub. (2013). OMIA:001443-9940: 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.
| 2023 | Mitchell, N.L., Russell, K.N., Barrell, G.K., Tammen, I., Palmer, D.N. : |
| Characterization of neuropathology in ovine CLN5 and CLN6 neuronal ceroid lipofuscinoses (Batten disease). Dev Neurobiol 83:127-142, 2023. Pubmed reference: 37246363. DOI: 10.1002/dneu.22918. | |
| Murray, S.J., Almuqbel, M.M., Felton, S.A., Palmer, N.J., Myall, D.J., Shoorangiz, R., Ella, A., Keller, M., Palmer, D.N., Melzer, T.R., Mitchell, N.L. : | |
| Progressive MRI brain volume changes in ovine models of CLN5 and CLN6 neuronal ceroid lipofuscinosis. Brain Commun 5:fcac339, 2023. Pubmed reference: 36632184. DOI: 10.1093/braincomms/fcac339. | |
| 2022 | Banstola, A., Reynolds, J.N.J. : |
| The sheep as a large animal model for the investigation and treatment of human disorders. Biology (Basel) 11:1251, 2022. Pubmed reference: 36138730. DOI: 10.3390/biology11091251. | |
| Barry, L.A., Kay, G.W., Mitchell, N.L., Murray, S.J., Jay, N.P., Palmer, D.N. : | |
| Aggregation chimeras provide evidence of in vivo intercellular correction in ovine CLN6 neuronal ceroid lipofuscinosis (Batten disease). PLoS One 17:e0261544, 2022. Pubmed reference: 35404973. DOI: 10.1371/journal.pone.0261544. | |
| 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. : | |
| Natural history of retinal degeneration in ovine models of CLN5 and CLN6 neuronal ceroid lipofuscinoses. Sci Rep 12:3670, 2022. Pubmed reference: 35256654. DOI: 10.1038/s41598-022-07612-7. | |
| 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. | |
| 2021 | Jolly, R.D., Dittmer, K.E., Jones, B.R., Worth, A.J., Thompson, K.G., Johnstone, A.C., Palmer, D.N., Van de Water, N.S., Hemsley, K.M., Garrick, D.J., Winchester, B.G., Walkley, S.U. : |
| Animal medical genetics: a historical perspective on more than 50 years of research into genetic disorders of animals at Massey University. N Z Vet J 69:255-266, 2021. Pubmed reference: 33969809. DOI: 10.1080/00480169.2021.1928564. | |
| Russell, K.N., Mitchell, N.L., Wellby, M.P., Barrell, G.K., Palmer, D.N. : | |
| Electroretinography data from ovine models of CLN5 and CLN6 neuronal ceroid lipofuscinoses. Data Brief 37:107188, 2021. Pubmed reference: 34141843. DOI: 10.1016/j.dib.2021.107188. | |
| 2018 | Russell, K.N., Mitchell, N.L., Anderson, N.G., Bunt, C.R., Wellby, M.P., Melzer, T.R., Barrell, G.K., Palmer, D.N. : |
| Computed tomography provides enhanced techniques for longitudinal monitoring of progressive intracranial volume loss associated with regional neurodegeneration in ovine neuronal ceroid lipofuscinoses. Brain Behav 8:e01096, 2018. Pubmed reference: 30136763. DOI: 10.1002/brb3.1096. | |
| 2016 | Cronin, G.M., Beganovic, D.F., Sutton, A.L., Palmer, D., Thomson, P.C., Tammen, I. : |
| Manifestation of neuronal ceroid lipofuscinosis in Australian Merino sheep: observations on altered behaviour and growth. Appl Anim Behav Sci 175:32-40, 2016. Pubmed reference: 26949278. DOI: 10.1016/j.applanim.2015.11.012. | |
| 2015 | Palmer, D.N., Neverman, N.J., Chen, J.Z., Chang, C.T., Houweling, P.J., Barry, L.A., Tammen, I., Hughes, S.M., Mitchell, N.L. : |
| Recent studies of ovine neuronal ceroid lipofuscinoses from BARN, the Batten Animal Research Network. Biochim Biophys Acta 1852:2279-86, 2015. Pubmed reference: 26073432. DOI: 10.1016/j.bbadis.2015.06.013. | |
| Sawiak, S.J., Perumal, S.R., Rudiger, S.R., Matthews, L., Mitchell, N.L., McLaughlan, C.J., Bawden, C.S., Palmer, D.N., Kuchel, T., Morton, A.J. : | |
| Rapid and Progressive Regional Brain Atrophy in CLN6 Batten Disease Affected Sheep Measured with Longitudinal Magnetic Resonance Imaging. PLoS One 10:e0132331, 2015. Pubmed reference: 26161747. DOI: 10.1371/journal.pone.0132331. | |
| 2014 | Grubman, A., Lidgerwood, G.E., Duncan, C., Bica, L., Tan, J.L., Parker, S.J., Caragounis, A., Meyerowitz, J., Volitakis, I., Moujalled, D., Liddell, J.R., Hickey, J.L., Horne, M., Longmuir, S., Koistinaho, J., Donnelly, P.S., Crouch, P.J., Tammen, I., White, A.R., Kanninen, K.M. : |
| Deregulation of subcellular biometal homeostasis through loss of the metal transporter, Zip7, in a childhood neurodegenerative disorder. Acta Neuropathol Commun 2:25, 2014. Pubmed reference: 24581221. DOI: 10.1186/2051-5960-2-25. | |
| 2013 | Bond, M., Holthaus, S.M., Tammen, I., Tear, G., Russell, C. : |
| Use of model organisms for the study of neuronal ceroid lipofuscinosis. Biochim Biophys Acta 1832:1842-65, 2013. Pubmed reference: 23338040. DOI: 10.1016/j.bbadis.2013.01.009. | |
| Kanninen, K.M., Grubman, A., Meyerowitz, J., Duncan, C., Tan, J.L., Parker, S.J., Crouch, P.J., Paterson, B.M., Hickey, J.L., Donnelly, P.S., Volitakis, I., Tammen, I., Palmer, D.N., White, A.R. : | |
| Increased zinc and manganese in parallel with neurodegeneration, synaptic protein changes and activation of Akt/GSK3 signaling in ovine CLN6 neuronal ceroid lipofuscinosis. PLoS One 8:e58644, 2013. Pubmed reference: 23516525. DOI: 10.1371/journal.pone.0058644. | |
| Kay, G.W., Palmer, D.N. : | |
| Chronic oral administration of minocycline to sheep with ovine CLN6 neuronal ceroid lipofuscinosis maintains pharmacological concentrations in the brain but does not suppress neuroinflammation or disease progression. J Neuroinflammation 10:97, 2013. Pubmed reference: 23899308. DOI: 10.1186/1742-2094-10-97. | |
| 2012 | Mohd Ismail, I.F., Mitchell, N.L., Hobbs, M., Cavanagh, J.A.L., Palmer, D.N., Tammen, I. : |
| Next generation sequencing identifies the disease causing mutation for NCL in South Hampshire sheep. 13th International Conference on Neuronal Ceroid Lipofuscinoses (Batten Disease), London, UK :p. 07, 2012. | |
| 2008 | Oswald, MJ., Palmer, DN., Kay, GW., Barwell, KJ., Cooper, JD. : |
| Location and connectivity determine GABAergic interneuron survival in the brains of South Hampshire sheep with CLN6 neuronal ceroid lipofuscinosis. Neurobiol Dis 32:50-65, 2008. Pubmed reference: 18634879. DOI: 10.1016/j.nbd.2008.06.004. | |
| 2007 | Pears, MR., Salek, RM., Palmer, DN., Kay, GW., Mortishire-Smith, RJ., Griffin, JL. : |
| Metabolomic investigation of CLN6 neuronal ceroid lipofuscinosis in affected South Hampshire sheep. J Neurosci Res 85:3494-504, 2007. Pubmed reference: 17510975. DOI: 10.1002/jnr.21343. | |
| 2006 | Tammen, I., Houweling, PJ., Frugier, T., Mitchell, NL., Kay, GW., Cavanagh, JA., Cook, RW., Raadsma, HW., Palmer, DN. : |
| A missense mutation (c.184C>T) in ovine CLN6 causes neuronal ceroid lipofuscinosis in Merino sheep whereas affected South Hampshire sheep have reduced levels of CLN6 mRNA. Biochim Biophys Acta 1762:898-905, 2006. Pubmed reference: 17046213. DOI: 10.1016/j.bbadis.2006.09.004. | |
| 2005 | Oswald, MJ., Palmer, DN., Kay, GW., Shemilt, SJ., Rezaie, P., Cooper, JD. : |
| Glial activation spreads from specific cerebral foci and precedes neurodegeneration in presymptomatic ovine neuronal ceroid lipofuscinosis (CLN6). Neurobiol Dis 20:49-63, 2005. Pubmed reference: 16137566. DOI: 10.1016/j.nbd.2005.01.025. | |
| 2002 | Cook, R.W., Jolly, R.D., Palmer, D.N., Tammen, I., Broom, M.F., McKinnon, R. : |
| Neuronal ceroid lipofuscinosis in Merino sheep Aust Vet J 80:292-7, 2002. Pubmed reference: 12074311. DOI: 10.1111/j.1751-0813.2002.tb10847.x. | |
| 2001 | Broom, MF., Zhou, C. : |
| Fine mapping of ovine ceroid lipofuscinosis confirms orthology with CLN6. Eur J Paediatr Neurol 5 Suppl A:33-5, 2001. Pubmed reference: 11589004. | |
| Tammen, I., Cook, RW., Nicholas, FW., Raadsma, HW. : | |
| Neuronal ceroid lipofuscinosis in Australian Merino sheep: a new animal model. Eur J Paediatr Neurol 5 Suppl A:37-41, 2001. Pubmed reference: 11589005. DOI: 10.1053/ejpn.2000.0432. | |
| 1999 | Broom, MF., Zhou, C., Hill, DF. : |
| Progress toward positional cloning of ovine neuronal ceroid lipofuscinosis, a model of the human late-infantile variant CLN6. Mol Genet Metab 66:373-5, 1999. Pubmed reference: 10191131. DOI: 10.1006/mgme.1999.2823. | |
| Jolly, R.D., Walkley, S.U. : | |
| Ovine ceroid lipofuscinosis (OCL6): Postulated mechanism of neurodegeneration Molecular Genetics & Metabolism 66:376-380, 1999. | |
| 1998 | Broom, M.F., Zhou, C.M., Broom, J.E., Barwell, K.J., Jolly, R.D., Hill, D.F. : |
| Ovine neuronal ceroid lipofuscinosis - a large animal model syntenic with the human neuronal ceroid lipofuscinosis variant CLN6 Journal of Medical Genetics 35:717-721, 1998. Pubmed reference: 9733028. | |
| 1992 | Goebel, H.H. : |
| Retina in various animal models of neuronal ceroid-lipofuscinosis. Am J Med Genet 42:605-8, 1992. Pubmed reference: 1609843. DOI: 10.1002/ajmg.1320420435. | |
| 1980 | Jolly, RD., Janmaat, A., West, DM., Morrison, I. : |
| Ovine ceroid-lipofuscinosis: a model of Batten's disease. Neuropathol Appl Neurobiol 6:195-209, 1980. Pubmed reference: 6772982. DOI: 10.1111/j.1365-2990.1980.tb00290.x. | |
| 1976 | Jolly, R. D., West, D. M. : |
| Blindness in South Hampshire sheep: a neuronal ceroid-lipofuscinosis New Zealand Veterinary Journal 24:123, 1976. Pubmed reference: 1067509. DOI: 10.1080/00480169.1976.34298. |
Edit History
- Created by Frank Nicholas on 05 Apr 2011
- Changed by Frank Nicholas on 08 Oct 2011
- Changed by Frank Nicholas on 09 Dec 2011
- Changed by Frank Nicholas on 20 Aug 2013