Intragenic MFSD8 duplication and histopathological findings in a rabbit with neuronal ceroid lipofuscinosis.
Oryctolagus cuniculus
Batten disease
animal model
hereditary disease
neurology
precision medicine
Journal
Animal genetics
ISSN: 1365-2052
Titre abrégé: Anim Genet
Pays: England
ID NLM: 8605704
Informations de publication
Date de publication:
07 May 2024
07 May 2024
Historique:
revised:
20
03
2024
received:
20
03
2024
accepted:
22
04
2024
medline:
7
5
2024
pubmed:
7
5
2024
entrez:
7
5
2024
Statut:
aheadofprint
Résumé
Neuronal ceroid lipofuscinoses (NCL) are among the most prevalent neurodegenerative disorders of early life in humans. Disease-causing variants have been described for 13 different NCL genes. In this study, a refined pathological characterization of a female rabbit with progressive neurological signs reminiscent of NCL was performed. Cytoplasmic pigment present in neurons was weakly positive with Sudan black B and autofluorescent. Immunohistology revealed astrogliosis, microgliosis and axonal degeneration. During the subsequent genetic investigation, the genome of the affected rabbit was sequenced and examined for private variants in NCL candidate genes. The analysis revealed a homozygous ~10.7 kb genomic duplication on chromosome 15 comprising parts of the MFSD8 gene, NC_013683.1:g.103,727,963_103,738,667dup. The duplication harbors two internal protein coding exons and is predicted to introduce a premature stop codon into the transcript, truncating ~50% of the wild-type MFSD8 open reading frame encoding the major facilitator superfamily domain containing protein 8, XP_002717309.2:p.(Glu235Leufs*23). Biallelic loss-of-function variants in MFSD8 have been described to cause NCL7 in human patients, dogs and a single cat. The available clinical and pathological data, together with current knowledge about MFSD8 variants and their functional impact in other species, point to the MFSD8 duplication as a likely causative defect for the observed phenotype in the affected rabbit.
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
© 2024 The Authors. Animal Genetics published by John Wiley & Sons Ltd on behalf of Stichting International Foundation for Animal Genetics.
Références
Amberger, J.S., Bocchini, C.A., Schiettecatte, F., Scott, A.F. & Hamosh, A. (2015) OMIM.org: Online Mendelian Inheritance in Man (OMIM®), an online catalog of human genes and genetic disorders. Nucleic Acids Research, 43(Database issue), D789–D798. Available from: https://doi.org/10.1093/nar/gku1205
Anderson, G.W., Goebel, H.H. & Simonati, A. (2013) Human pathology in NCL. Biochimica et Biophysica Acta, 1832(11), 1807–1826. Available from: https://doi.org/10.1016/j.bbadis.2012.11.014
Ashwini, A., D'Angelo, A., Yamato, O., Giordano, C., Cagnotti, G., Harcourt‐Brown, T. et al. (2016) Neuronal ceroid lipofuscinosis associated with an MFSD8 mutation in Chihuahuas. Molecular Genetics and Metabolism, 118(4), 326–332. Available from: https://doi.org/10.1016/j.ymgme.2016.05.008
Barker, E., Morgan, A. & Barclay, J.W. (2023) A Caenorhabditis elegans model of autosomal dominant adult‐onset neuronal ceroid lipofuscinosis identifies ethosuximide as a potential therapeutic. Human Molecular Genetics, 32(11), 1772–1785. Available from: https://doi.org/10.1093/hmg/ddac263
Bond, M., Holthaus, S.‐M.K., Tammen, I., Tear, G. & Russell, C. (2013) Use of model organisms for the study of neuronal ceroid lipofuscinosis. Biochimica et Biophysica Acta (BBA) – Molecular Basis of Disease, 1832(11), 1842–1865. Available from: https://doi.org/10.1016/j.bbadis.2013.01.009
Böttcher‐Künneke, A., Gregor, K., Baumgärtner, W. & Puff, C. (2020) Neuronale Speicherkrankheit bei einem ausgewachsenen weiblichen Kaninchen. Kleintierpraxis, 65(12), 656–665. Available from: https://doi.org/10.2377/0023‐2076‐65‐656
Brandenstein, L., Schweizer, M., Sedlacik, J., Fiehler, J. & Storch, S. (2016) Lysosomal dysfunction and impaired autophagy in a novel mouse model deficient for the lysosomal membrane protein Cln7. Human Molecular Genetics, 25(4), 777–791. Available from: https://doi.org/10.1093/hmg/ddv615
Bullock, G., Johnson, G.S., Mhlanga‐Mutangadura, T., Petesch, S.C., Thompson, S., Goebbels, S. et al. (2022) Lysosomal storage disease associated with a CNP sequence variant in Dalmatian dogs. Gene, 830, 146513. Available from: https://doi.org/10.1016/j.gene.2022.146513
Cesta, M.F., Mozzachio, K., Little, P.B., Olby, N.J., Sills, R.C. & Brown, T.T. (2006) Neuronal ceroid lipofuscinosis in a Vietnamese pot‐bellied pig (Sus scrofa). Veterinary Pathology, 43(4), 556–560. Available from: https://doi.org/10.1354/vp.43‐4‐556
Chalkley, M.D., Armien, A.G., Gilliam, D.H., Johnson, G.S., Zeng, R., Wünschmann, A. et al. (2014) Characterization of neuronal ceroid‐lipofuscinosis in 3 cats. Veterinary Pathology, 51(4), 796–804. Available from: https://doi.org/10.1177/0300985813502818
Cingolani, P., Platts, A., Wang, L.L., Coon, M., Nguyen, T., Wang, L. et al. (2012) A program for annotating and predicting the effects of single nucleotide polymorphisms, SnpEff. Fly, 6(2), 80–92. Available from: https://doi.org/10.4161/fly.19695
Damme, M., Brandenstein, L., Fehr, S., Jankowiak, W., Bartsch, U., Schweizer, M. et al. (2014) Gene disruption of Mfsd8 in mice provides the first animal model for CLN7 disease. Neurobiology of Disease, 65, 12–24. Available from: https://doi.org/10.1016/j.nbd.2014.01.003
Doboși, A.A., Bel, L.V., Paștiu, A.I. & Pusta, D.L. (2022) A review of Encephalitozoon cuniculi in domestic rabbits (Oryctolagus cuniculus) – biology, clinical signs, diagnostic techniques, treatment, and prevention. Pathogens, 11(12), 1486. Available from: https://doi.org/10.3390/pathogens11121486
Faller, K.M.E., Bras, J., Sharpe, S.J., Anderson, G.W., Darwent, L., Kun‐Rodrigues, C. et al. (2016) The Chihuahua dog: a new animal model for neuronal ceroid lipofuscinosis CLN7 disease? Journal of Neuroscience Research, 94(4), 339–347. Available from: https://doi.org/10.1002/jnr.23710
Guevar, J., Hug, P., Giebels, F., Durand, A., Jagannathan, V. & Leeb, T. (2020) A major facilitator superfamily domain 8 frameshift variant in a cat with suspected neuronal ceroid lipofuscinosis. Journal of Veterinary Internal Medicine, 34(1), 289–293. Available from: https://doi.org/10.1111/jvim.15663
Guo, J., Johnson, G.S., Cook, J., Harris, O.K., Mhlanga‐Mutangadura, T., Schnabel, R.D. et al. (2019) Neuronal ceroid lipofuscinosis in a German shorthaired pointer associated with a previously reported CLN8 nonsense variant. Molecular Genetics and Metabolism Reports, 21, 100521. Available from: https://doi.org/10.1016/j.ymgmr.2019.100521
Guo, J., O'Brien, D.P., Mhlanga‐Mutangadura, T., Olby, N.J., Taylor, J.F., Schnabel, R.D. et al. (2015) A rare homozygous MFSD8 single‐base‐pair deletion and frameshift in the whole genome sequence of a Chinese crested dog with neuronal ceroid lipofuscinosis. BMC Veterinary Research, 10(1), 960. Available from: https://doi.org/10.1186/s12917‐014‐0181‐z
Huang, B., Zdora, I., de Buhr, N., Lehmbecker, A., Baumgärtner, W. & Leitzen, E. (2021) Phenotypical peculiarities and species‐specific differences of canine and murine satellite glial cells of spinal ganglia. Journal of Cellular and Molecular Medicine, 25(14), 6909–6924. Available from: https://doi.org/10.1111/jcmm.16701
Huber, R.J., Hughes, S.M., Liu, W., Morgan, A., Tuxworth, R.I. & Russell, C. (2020) The contribution of multicellular model organisms to neuronal ceroid lipofuscinosis research. Biochimica et Biophysica Acta – Molecular Basis of Disease, 1866(9), 165614. Available from: https://doi.org/10.1016/j.bbadis.2019.165614
Jagannathan, V., Drögemüller, C., Leeb, T., Aguirre, G., André, C., Bannasch, D. et al. (2019) A comprehensive biomedical variant catalogue based on whole genome sequences of 582 dogs and eight wolves. Animal Genetics, 50(6), 695–704. Available from: https://doi.org/10.1111/age.12834
Karli, P., Oevermann, A., Bauer, A., Jagannathan, V. & Leeb, T. (2016) MFSD8 single‐base pair deletion in a Chihuahua with neuronal ceroid lipofuscinosis. Animal Genetics, 47(5), 631. Available from: https://doi.org/10.1111/age.12449
Katz, M.L., Buckley, R.M., Biegen, V., O'Brien, D.P., Johnson, G.C., Warren, W.C. et al. (2020) Neuronal ceroid lipofuscinosis in a domestic cat associated with a DNA sequence variant that creates a premature stop codon in CLN6. G3: Genes, Genomes, Genetics, 10(8), 2741–2751. Available from: https://doi.org/10.1534/g3.120.401407
McBride, J.L., Neuringer, M., Ferguson, B., Kohama, S.G., Tagge, I.J., Zweig, R.C. et al. (2018) Discovery of a CLN7 model of Batten disease in non‐human primates. Neurobiology of Disease, 119, 65–78. Available from: https://doi.org/10.1016/j.nbd.2018.07.013
McKenna, A., Hanna, M., Banks, E., Sivachenko, A., Cibulskis, K., Kernytsky, A. et al. (2010) The Genome Analysis Toolkit: a MapReduce framework for analyzing next‐generation DNA sequencing data. Genome Research, 20(9), 1297–1303. Available from: https://doi.org/10.1101/gr.107524.110
Mole, S.E., Anderson, G., Band, H.A., Berkovic, S.F., Cooper, J.D., Kleine Holthaus, S.‐M. et al. (2019) Clinical challenges and future therapeutic approaches for neuronal ceroid lipofuscinosis. The Lancet Neurology, 18(1), 107–116. Available from: https://doi.org/10.1016/S1474‐4422(18)30368‐5
Nibe, K., Miwa, Y., Matsunaga, S., Chambers, J.K., Uetsuka, K., Nakayama, H. et al. (2011) Clinical and pathologic features of neuronal ceroid‐lipofuscinosis in a ferret (Mustela putorius furo). Veterinary Pathology, 48(6), 1185–1189. Available from: https://doi.org/10.1177/0300985811400441
Nicholas, F., Tammen, I. & Sydney Informatics Hub. (1995) Online Mendelian inheritance in animals (OMIA). Sydney, NSW: The University of Sydney. Available from: https://doi.org/10.25910/2amr‐pv70
Nita, D.A., Mole, S.E. & Minassian, B.A. (2016) Neuronal ceroid lipofuscinoses. Epileptic Disorders, 18(S2), 73–88. Available from: https://doi.org/10.1684/epd.2016.0844
Nittari, G., Tomassoni, D., Roy, P., Martinelli, I., Tayebati, S.K. & Amenta, F. (2023) Batten disease through different in vivo and in vitro models: a review. Journal of Neuroscience Research, 101(3), 298–315. Available from: https://doi.org/10.1002/jnr.25147
Nolte, A., Bello, A., Drögemüller, M., Leeb, T., Brockhaus, E., Baumgärtner, W. et al. (2016) Neuronal ceroid lipofuscinosis in an adult American Staffordshire terrier. Tierarztliche Praxis Ausgabe K: Kleintiere/Heimtiere, 44(6), 431–437. Available from: https://doi.org/10.15654/TPK‐150766
Parenti, G., Andria, G. & Ballabio, A. (2015) Lysosomal storage diseases: from pathophysiology to therapy. Annual Review of Medicine, 66(1), 471–486. Available from: https://doi.org/10.1146/annurev‐med‐122313‐085916
Platt, F.M., D'Azzo, A., Davidson, B.L., Neufeld, E.F. & Tifft, C.J. (2018) Lysosomal storage diseases. Nature Reviews Disease Primers, 4(1), 27. Available from: https://doi.org/10.1038/s41572‐018‐0025‐4
Qureshi, Y.H., Baez, P. & Reitz, C. (2020) Endosomal trafficking in Alzheimer's disease, Parkinson's disease, and neuronal ceroid lipofuscinosis. Molecular and Cellular Biology, 40(19), 1–12. Available from: https://doi.org/10.1128/MCB.00262‐20
Rickmeyer, T., Schöniger, S., Petermann, A., Harzer, K., Kustermann‐Kuhn, B., Fuhrmann, H. et al. (2013) GM2 gangliosidosis in an adult pet rabbit. Journal of Comparative Pathology, 148(2–3), 243–247. Available from: https://doi.org/10.1016/j.jcpa.2012.06.008
Robles, L.J. (1978) Accumulation and identification of lipofuscin‐like pigment in the neurons of Bulla gouldiana (Gastropoda: Opisthobranchia). Mechanisms of Ageing and Development, 7(1), 53–64. Available from: https://doi.org/10.1016/0047‐6374(78)90052‐0
Schulz, A., Kohlschütter, A., Mink, J., Simonati, A. & Williams, R. (2013) NCL diseases – clinical perspectives. Biochimica et Biophysica Acta, 1832(11), 1801–1806. Available from: https://doi.org/10.1016/j.bbadis.2013.04.008
Sharifi, A., Kousi, M., Sagné, C., Bellenchi, G.C., Morel, L., Darmon, M. et al. (2010) Expression and lysosomal targeting of CLN7, a major facilitator superfamily transporter associated with variant late‐infantile neuronal ceroid lipofuscinosis. Human Molecular Genetics, 19(22), 4497–4514. Available from: https://doi.org/10.1093/hmg/ddq381
Siintola, E., Topcu, M., Aula, N., Lohi, H., Minassian, B.A., Paterson, A.D. et al. (2007) The novel neuronal ceroid lipofuscinosis gene MFSD8 encodes a putative lysosomal transporter. The American Journal of Human Genetics, 81(1), 136–146. Available from: https://doi.org/10.1086/518902
Specchio, N., Ferretti, A., Trivisano, M., Pietrafusa, N., Pepi, C., Calabrese, C. et al. (2021) Neuronal ceroid lipofuscinosis: potential for targeted therapy. Drugs, 81(1), 101–123. Available from: https://doi.org/10.1007/s40265‐020‐01440‐7
Story, B.D., Miller, M.E., Bradbury, A.M., Million, E.D., Duan, D., Taghian, T. et al. (2020) Canine models of inherited musculoskeletal and neurodegenerative diseases. Frontiers in Veterinary Science, 7, 1–21. Available from: https://doi.org/10.3389/fvets.2020.00080
Swier, V.J., White, K.A., Johnson, T.B., Sieren, J.C., Johnson, H.J., Knoernschild, K. et al. (2022) A novel porcine model of CLN2 batten disease that recapitulates patient phenotypes. Neurotherapeutics, 19(6), 1905–1919. Available from: https://doi.org/10.1007/s13311‐022‐01296‐7
Villani, N.A., Bullock, G., Michaels, J.R., Yamato, O., O'Brien, D.P., Mhlanga‐Mutangadura, T. et al. (2019) A mixed breed dog with neuronal ceroid lipofuscinosis is homozygous for a CLN5 nonsense mutation previously identified in Border Collies and Australian cattle dogs. Molecular Genetics and Metabolism, 127(1), 107–115. Available from: https://doi.org/10.1016/j.ymgme.2019.04.003
Wei‐Lin Popp, M. & Maquat, L.E. (2013) Organizing principles of mammalian nonsense‐mediated mRNA decay. Annual Review of Genetics, 47, 139–165. Available from: https://doi.org/10.1146/annurev‐genet‐111212‐133424
Ziehl, F. (1882) Zur Färbung des Tuberkelbacillus. DMW – Deutsche Medizinische Wochenschrift, 8(33), 451. Available from: https://doi.org/10.1055/s‐0029‐1196721