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H., 2009\nCarcel-Trullols, J., Kovacs, A. D., & Pearce, D. A. (2015). Cell biology of the NCL proteins: What they do and don't do. Biochim. Biophys. Acta, 1852(10 Pt B), 2242-2255. doi:https:\u002F\u002Fdoi.org\u002F10.1016\u002Fj.bbadis.2015.04.027.\nCingolani, 2012, A program for annotating and predicting the effects of single nucleotide polymorphisms, SnpEff: SNPs in the genome of Drosophila melanogaster strain w1118; iso-2; iso-3, Fly (Austin), 6, 80, 10.4161\u002Ffly.19695\nCooper, 2015, Towards a new understanding of NCL pathogenesis, Biochim. Biophys. Acta, 1852, 2256, 10.1016\u002Fj.bbadis.2015.05.014\nCraiu, 2015, Rett-like onset in late-infantile neuronal ceroid lipofuscinosis (CLN7) caused by compound heterozygous mutation in the MFSD8 gene and review of the literature data on clinical onset signs, Eur. J. Paediatr. Neurol., 19, 78, 10.1016\u002Fj.ejpn.2014.07.008\nDamme, 2014, Gene disruption of Mfsd8 in mice provides the first animal model for CLN7 disease, Neurobiol. Dis., 65, 12, 10.1016\u002Fj.nbd.2014.01.003\nDepristo, 2011, A framework for variation discovery and genotyping using next-generation DNA sequencing data, Nat. Genet., 43, 491, 10.1038\u002Fng.806\nFaller, 2016, The Chihuahua dog: A new animal model for neuronal ceroid lipofuscinosis CLN7 disease?, J. Neurosci. Res., 94, 339, 10.1002\u002Fjnr.23710\nGuo, 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 Vet. Res., 10, 960, 10.1186\u002Fs12917-014-0181-z\nHood, 2012, ISCEV standard for clinical multifocal electroretinography (mfERG) (2011 edition), Doc. Ophthalmol., 124, 1, 10.1007\u002Fs10633-011-9296-8\nJankowiak, 2016, Retinal degeneration in mice deficient in the lysosomal membrane protein CLN7, Invest. Ophthalmol. Vis. Sci., 57, 4989, 10.1167\u002Fiovs.16-20158\nJenkinson, 2012, Fsl, Neuroimage, 62, 782, 10.1016\u002Fj.neuroimage.2011.09.015\nKhan, 2017, Specific alleles of CLN7\u002FMFSD8, a protein that localizes to photoreceptor synaptic terminals, cause a spectrum of nonsyndromic retinal dystrophy, Invest. Ophthalmol. Vis. Sci., 58, 2906, 10.1167\u002Fiovs.16-20608\nKoilkonda, 2014, Safety and effects of the vector for the Leber hereditary optic neuropathy gene therapy clinical trial, JAMA Ophthalmol., 132, 409, 10.1001\u002Fjamaophthalmol.2013.7630\nKousi, 2009, Mutations in CLN7\u002FMFSD8 are a common cause of variant late-infantile neuronal ceroid lipofuscinosis, Brain, 132, 810, 10.1093\u002Fbrain\u002Fawn366\nKousi, 2012, Update of the mutation spectrum and clinical correlations of over 360 mutations in eight genes that underlie the neuronal ceroid lipofuscinoses, Hum. Mutat., 33, 42, 10.1002\u002Fhumu.21624\nLi, 2013\nMcGill, 2016, Elevated Fundus Autofluorescence in Monkeys Deficient in Lutein, Zeaxanthin, and Omega-3 Fatty Acids, Invest. Ophthalmol. Vis. Sci., 57, 1361, 10.1167\u002Fiovs.15-18596\nMcKenna, 2010, The Genome Analysis Toolkit: a MapReduce framework for analyzing next-generation DNA sequencing data, Genome Res., 20, 1297, 10.1101\u002Fgr.107524.110\nOstergaard, 2011, Cardiac involvement in juvenile neuronal ceroid lipofuscinosis (Batten disease), Neurology, 76, 1245, 10.1212\u002FWNL.0b013e31821435bd\nPalmer, 2013, NCL disease mechanisms, Biochim. Biophys. Acta, 1832, 1882, 10.1016\u002Fj.bbadis.2013.05.014\nRadke, 2015, Human NCL neuropathology, Biochim. Biophys. Acta, 1852, 2262, 10.1016\u002Fj.bbadis.2015.05.007\nShacka, 2012, Mouse models of neuronal ceroid lipofuscinoses: useful pre-clinical tools to delineate disease pathophysiology and validate therapeutics, Brain Res. 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1981, Thresholds in cerebral ischemia-the ischemic penumbra, Stroke, 12, 723, 10.1161\u002F01.STR.12.6.723\nBederson, 1986, Evaluation of 2,3,5-triphenyltetrazolium chloride as a stain for detection and quantification of experimental cerebral infarction in rats, Stroke, 17, 1304, 10.1161\u002F01.STR.17.6.1304\nChoi, 1997, Background genes: Out of sight, but not out of brain, Trends Neurosci., 20, 499\nConnolly, 1996, Procedural and strain-related variables significantly affect outcome in a murine model of focal cerebral ischemia, Neurosurgery, 38, 523\nCoyle, 1987, Spatial relations of dorsal anastomoses and lesion border after middle cerebral artery occlusion, Stroke, 18, 1133, 10.1161\u002F01.STR.18.6.1133\nCoyle, 1982, Dorsal cerebral arterial collaterals of the rat, Anat. Rec., 203, 397, 10.1002\u002Far.1092030309\nFujii, 1997, Strain-related differences in susceptibility to transient forebrain ischemia in SV-129 and C57Black\u002F6 mice, Stroke, 28, 1805, 10.1161\u002F01.STR.28.9.1805\nGerlai, 1996, Gene-targeting studies of mammalian behavior: Is it the mutation or the background genotype, Trends Neurosci., 19, 177, 10.1016\u002FS0166-2236(96)20020-7\nHara, 1996, Reduced brain edema and infarction volume in mice lacking the neuronal isoform of nitric oxide synthase after transient MCA occlusion, J. Cereb. Blood Flow Metab., 16, 605, 10.1097\u002F00004647-199607000-00010\nHata, 1998, A reproducible model of middle cerebral artery occlusion in mice: Hemodynamic, biochemical, and magnetic resonance imaging, J. Cereb. Blood Flow Metab., 18, 367, 10.1097\u002F00004647-199804000-00004\nHossmann, 1993, Collateral circulation of the brain\nKitagawa, 1998, Cerebral ischemia after bilateral carotid artery occlusion and intraluminal suture occlusion in mice: Evaluation of the patency of the posterior communicating artery, J. Cereb. Blood Flow Metab., 18, 570, 10.1097\u002F00004647-199805000-00012\nKogure, 1978, A pictorial representation of endogenous brain ATP by a bioluminescent method, Brain Res., 154, 273, 10.1016\u002F0006-8993(78)90700-X\nMaeda, 1998, Differences in the cerebrovascular anatomy of C57Black\u002F6 and SV129 mice, NeuroReport, 9, 1317, 10.1097\u002F00001756-199805110-00012\nMies, 1991, Ischemic thresholds of cerebral protein synthesis and energy state following middle cerebral artery occlusion in rat, J. Cereb. Blood Flow Metab., 11, 753, 10.1038\u002Fjcbfm.1991.132\nOliff, 1997, Rat strain and vendor differences in collateral anastomoses, J. Cereb. 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Mol. Genet., 14, 565, 10.1093\u002Fhmg\u002Fddi053\nBjorkqvist, 2006, Progressive alterations in the hypothalamic–pituitary–adrenal axis in the R6\u002F2 transgenic mouse model of Huntington’s disease, Hum. Mol. Genet., 15, 1713, 10.1093\u002Fhmg\u002Fddl094\nChan, 2002, Increased huntingtin protein length reduces the number of polyglutamine-induced gene expression changes in mouse models of Huntington’s disease, Hum. Mol. Genet., 11, 1939, 10.1093\u002Fhmg\u002F11.17.1939\nDavies, 1997, Formation of neuronal intranuclear inclusions underlies the neurological dysfunction in mice transgenic for the HD mutation, Cell, 90, 537, 10.1016\u002FS0092-8674(00)80513-9\nFarrer, 1985, Diabetes mellitus in Huntington disease, Clin. Genet., 27, 62, 10.1111\u002Fj.1399-0004.1985.tb00185.x\nFusco, 1999, Cellular localization of huntingtin in striatal and cortical neurons in rats: lack of correlation with neuronal vulnerability in Huntington’s disease, J. Neurosci., 19, 1189, 10.1523\u002FJNEUROSCI.19-04-01189.1999\nGauthier, 2004, Huntingtin controls neurotrophic support and survival of neurons by enhancing BDNF vesicular transport along microtubules, Cell, 118, 127, 10.1016\u002Fj.cell.2004.06.018\nGunawardena, 2003, Disruption of axonal transport by loss of huntingtin or expression of pathogenic polyQ proteins in Drosophila, Neuron, 40, 25, 10.1016\u002FS0896-6273(03)00594-4\nGuo, 2003, In silico analysis indicates a similar gene expression pattern between human brain and testis, Cytogenet. Genome Res., 103, 58, 10.1159\u002F000076290\nGutekunst, 1999, Nuclear and neuropil aggregates in Huntington’s disease: relationship to neuropathology, J. Neurosci., 19, 2522, 10.1523\u002FJNEUROSCI.19-07-02522.1999\nGuttman, 2000, Dynein and plus-end microtubule-dependent motors are associated with specialized Sertoli cell junction plaques (ectoplasmic specializations), J. Cell Sci., 113, 2167, 10.1242\u002Fjcs.113.12.2167\nHall, 1992, Distribution of the microtubule-dependent motors cytoplasmic dynein and kinesin in rat testis, Biol. Reprod., 46, 817, 10.1095\u002Fbiolreprod46.5.817\nHarper, P., 1996. Huntington’s disease, 2.\nHayden, M.R., 1981. Huntington’s chorea.\nHurlbert, 1999, Mice transgenic for an expanded CAG repeat in the Huntington’s disease gene develop diabetes, Diabetes, 48, 649, 10.2337\u002Fdiabetes.48.3.649\nKremer, 1990, Atrophy of the hypothalamic lateral tuberal nucleus in Huntington’s disease, J. Neuropathol. Exp. Neurol., 49, 371, 10.1097\u002F00005072-199007000-00002\nKremer, 1991, The hypothalamic lateral tuberal nucleus and the characteristics of neuronal loss in Huntington’s disease, Neurosci. Lett., 132, 101, 10.1016\u002F0304-3940(91)90443-W\nLavin, 1981, Studies of hypothalamic function in Huntington’s chorea, J. Neurol. Neurosurg. Psychiatry, 44, 414, 10.1136\u002Fjnnp.44.5.414\nLeavitt, 2001, Wild-type huntingtin reduces the cellular toxicity of mutant huntingtin in vivo, Am. J. Hum. Genet., 68, 313, 10.1086\u002F318207\nLuthi-Carter, 2002, Dysregulation of gene expression in the R6\u002F2 model of polyglutamine disease: parallel changes in muscle and brain, Hum. Mol. Genet., 11, 1911, 10.1093\u002Fhmg\u002F11.17.1911\nMacdonald, 1993, A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntingtons-disease chromosomes, Cell, 72, 971, 10.1016\u002F0092-8674(93)90585-E\nMangiarini, 1996, Exon 1 of the HD gene with an expanded CAG repeat is sufficient to cause a progressive neurological phenotype in transgenic mice, Cell, 87, 493, 10.1016\u002FS0092-8674(00)81369-0\nMarkianos, 2005, Plasma testosterone in male patients with Huntington’s disease: relations to severity of illness and dementia, Ann. Neurol., 57, 520, 10.1002\u002Fana.20428\nMastromauro, 1989, Estimation of fertility and fitness in Huntington disease in New England, Am. J. Med. Genet., 33, 248, 10.1002\u002Fajmg.1320330222\nMiller, 1999, Rat testis motor proteins associated with spermatid translocation (dynein) and spermatid flagella (kinesin-II), Biol. Reprod., 60, 1047, 10.1095\u002Fbiolreprod60.4.1047\nMuir, 2001, Enzyme immunoassay of 17 beta-estradiol, estrone conjugates, and testosterone in urinary and fecal samples from male and female mice, Horm. Metab Res., 33, 653, 10.1055\u002Fs-2001-18692\nPapalexi, 2005, Reduction of GnRH and infertility in the R6\u002F2 mouse model of Huntington’s disease, Eur. J. Neurosci., 22, 1541, 10.1111\u002Fj.1460-9568.2005.04324.x\nPetersen, 2005, Orexin loss in Huntington’s disease, Hum. Mol. Genet., 14, 39, 10.1093\u002Fhmg\u002Fddi004\nPodolsky, 1972, Increased frequency of diabetes mellitus in patients with Huntington’s chorea, Lancet, 1, 1356, 10.1016\u002FS0140-6736(72)91092-6\nPridmore, 1991, The fertility of HD-affected individuals in Tasmania, Aust. N. Z. J. Psychiatry, 25, 262, 10.1080\u002F00048679109077743\nRibchester, 2004, Progressive abnormalities in skeletal muscle and neuromuscular junctions of transgenic mice expressing the Huntington’s disease mutation, Eur. J. Neurosci., 20, 3092, 10.1111\u002Fj.1460-9568.2004.03783.x\nRussell, 1981, Effect of the microtubule disrupting agents, colchicine and vinblastine, on seminiferous tubule structure in the rat, Tissue Cell, 13, 349, 10.1016\u002F0040-8166(81)90010-0\nSathasivam, 1999, Formation of polyglutamine inclusions in non-CNS tissue, Hum. Mol. Genet., 8, 813, 10.1093\u002Fhmg\u002F8.5.813\nSelva, 2000, Meiotic arrest and germ cell apoptosis in androgen-binding protein transgenic mice, Endocrinology, 141, 1168, 10.1210\u002Fendo.141.3.7383\nSelva, 2004, The ATP-binding cassette transporter 1 mediates lipid efflux from Sertoli cells and influences male fertility, J. Lipid Res., 45, 1040, 10.1194\u002Fjlr.M400007-JLR200\nShokeir, 1975, Investigation on Huntington’s disease in the Canadian Prairies II. Fecundity and fitness, Clin. Genet., 7, 349, 10.1111\u002Fj.1399-0004.1975.tb00341.x\nSlow, 2003, Selective striatal neuronal loss in a YAC128 mouse model of Huntington disease, Hum. Mol. Genet., 12, 1555, 10.1093\u002Fhmg\u002Fddg169\nSlow, 2005, Absence of behavioral abnormalities and neurodegeneration in vivo despite widespread neuronal huntingtin inclusions, Proc. Natl. Acad. Sci. U. S. A., 102, 11402, 10.1073\u002Fpnas.0503634102\nStrand, 2005, Gene expression in Huntington’s disease skeletal muscle: a potential biomarker, Hum. Mol. Genet., 14, 1863, 10.1093\u002Fhmg\u002Fddi192\nSugars, 2003, Transcriptional abnormalities in Huntington disease, Trends Genet., 19, 233, 10.1016\u002FS0168-9525(03)00074-X\nSzebenyi, 2003, Neuropathogenic forms of huntingtin and androgen receptor inhibit fast axonal transport, Neuron, 40, 41, 10.1016\u002FS0896-6273(03)00569-5\nTrushina, 2004, Mutant huntingtin impairs axonal trafficking in mammalian neurons in vivo and in vitro, Mol. Cell. Biol., 24, 8195, 10.1128\u002FMCB.24.18.8195-8209.2004\nVan Raamsdonk, 2005, Selective degeneration and nuclear localization of mutant huntingtin in the YAC128 mouse model of Huntington disease, Hum. Mol. Genet., 14, 3823, 10.1093\u002Fhmg\u002Fddi407\nVan Raamsdonk, 2005, Loss of wild-type huntingtin influences motor dysfunction and survival in the YAC128 mouse model of Huntington disease, Hum. 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