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

Considered a defect: 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


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 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 g.16039510G>A c.184C>T 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].


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