Abstract
Infantile neuroaxonal dystrophy (INAD) is a rare autosomal recessive hereditary neurodegenerative disease of humans. So far, no responsible gene has been cloned or mapped to any chromosome. For chromosome mapping and positional cloning of the responsible gene, establishment of an animal model would be useful. Here we describe a new mouse model for INAD, named inad mouse. In this mouse, the phenotype is inherited in an autosomal recessive manner, symptoms occur in the infantile period, and the mouse dies before sexual maturity. Axonal dystrophic change appearing as spheroid bodies in central and peripheral nervous system was observed. These features more closely resembled human INAD than did those of the gad mouse, the traditional mouse model for INAD. Linkage analysis linked the inad gene to mouse Chromosome 1, with the highest LOD score (=128.6) at the D1Mit45 marker, and haplotype study localized the inad gene to a 7.5-Mb region between D1Mit84 and D1Mit25. In this linkage area some 60 genes exist: Mutation of one of these 60 genes is likely responsible for the inad mouse phenotype. Our preliminary mutation analysis in 15 genes examining the nucleotide sequence of exons of these genes did not find any sequence difference between inad mouse and C57BL/6 mouse.
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References
J Aicardi P Castelein (1979) ArticleTitleInfantile neuroaxonal dystrophy Brain 102 727–748 Occurrence Handle1:STN:280:Bi%2BD28nkt1c%3D Occurrence Handle509195
F Bohnhomme J-L Guénet (1989) The wild house mouse and its relatives MF Lyon AG Searlc (Eds) Genetic Variants and Strains of the Laboratory Mouse EditionNumber2nd ed. Oxford University Press Oxford 649–662
H Ceulemans A Eynde ParticleVan E Pérez-Callejón M Beullens W Stalmans et al. (1999) ArticleTitleStructure and splice products of the human gene encoding sds22, a putative mitotic regulator of protein phosphatase-1 Eur J Biochem 262 36–42 Occurrence Handle10.1046/j.1432-1327.1999.00344.x Occurrence Handle1:CAS:528:DyaK1MXjsVyqsbc%3D Occurrence Handle10231361
D Cowen EV Olmstead (1963) ArticleTitleInfantile neuroaxonal dystrophy J Neuropathol Exp Neurol 22 175–236 Occurrence Handle1:STN:280:CC2B3MrltVU%3D Occurrence Handle14023529
N Gordon (2002) ArticleTitleInfantile neuroaxonal dystrophy (Seitelberger’s disease) Dev Med Child Neurol 44 849–851 Occurrence Handle10.1017/S0012162201003036 Occurrence Handle12455862
L Karthikeyan M Flad M Engel B Meyer–Puttlitz RU Margolis et al. (1994) ArticleTitleImmunocytochemical and in situ hybridization studies of the heparin sulfate proteoglycan, glypican, in nervous tissue J Cell Sci 107 3213–3222 Occurrence Handle1:CAS:528:DyaK2MXisFSkt7Y%3D Occurrence Handle7699018
L Karthikeyan P Maurel U Rauch RK Margolis RU Margolis (1992) ArticleTitleCloning of major heparin sulfate proteoglycan from brain and identification as the rat form of glypican Biochem Biophys Res Commun 188 395–401 Occurrence Handle10.1016/0006-291X(92)92398-H Occurrence Handle1:CAS:528:DyaK3sXks1Grurg%3D Occurrence Handle1417860
KF Manly RH Cudmore SuffixJr JM Meer (2001) ArticleTitleMap Manager QTX, cross-platform software for genetic mapping Mamm Genome 12 930–932 Occurrence Handle10.1007/s00335-001-1016-3 Occurrence Handle1:CAS:528:DC%2BD3MXosFGgtbo%3D Occurrence Handle11707780
K Oda K Yamazaki H Miura H Shibasaki T Kikuchi (1992) ArticleTitleDying-back-type axonal degeneration of sensory nerve terminals in muscle spindles of the gracile axonal dystrophy (GAD) mutant mouse Neuropathol Appl Biol 128 265–281
Seitelberger F (1952) Eine unbekante Form von infantiler lipodispoidspeicher Krankheit des Gehirns. Proceedings of First International Neurological Congress of Neuropathology, Rome, 8–13 Sept 1952 (Turin: Rosenberg and Sellier), Vol 3, pp 323–333
K Yamazaki N Wakasugi T Tomita T Kikuchi M Mukoyama et al. (1988) ArticleTitleGracile axonal dystrophy (GAD), a new neurological mutant in the mouse Proc Exp Soc Exp Biol Med 187 209–215 Occurrence Handle1:STN:280:BieC38rgslE%3D
K Yamazaki A Sakakibara T Tomita M Mukoyama K Ando (1987) ArticleTitleLocation of gracile axonal dystrophy (gad) on chromosome 5 of the mouse Jpn J Genet 62 479–484
Acknowledgments
This research was supported in part by Kawano Masanori Memorial Foundation. This work was performed as a part of the Rational Evolutionary Design of Advanced Biomolecules (REDS) Project, Saitama Prefecture Collaboration of Regional Entities for the Advancement of Technological Excellence supported by JST. We thank Y. Asoh, J. Eguchi, Y. Taniguchi, R. Sekine, E. Tagawa, T. Shibuya, Y. Hoshi, K. Takahashi, T. Kaneko, Y. Seino, H. Enomoto, and A. Matsumura for their technical assistance. We also thank Dr. M. I. Tachibana and Mr. T. Walker for their editorial assistance and English translation.
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Matsushima, Y., Kikuchi, T., Kikuchi, H. et al. A new mouse model for infantile neuroaxonal dystrophy,inad mouse, maps to mouse Chromosome 1. Mamm Genome 16, 73–78 (2005). https://doi.org/10.1007/s00335-004-3017-5
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DOI: https://doi.org/10.1007/s00335-004-3017-5