特性など: |
生後15日頃より運動失調、歩行異常、転倒、後肢の伸長等が観察される(Takeuchi, 1991)。これらの表現型は常染色体劣性遺伝し、原因遺伝子はgroggy(gry)と名付けられた。生後60日以降より、小脳の縮小、組織学的に神経線維変性や神経細胞変性が中枢神経系に確認される。電子顕微鏡では小脳核、前庭核、薄束核の軸策終末部やシナプス全軸策に同心円状ラメラ小体が、高齢になると小脳核に多数のプルキンエ細胞の軸策腫大が観察される(Takeuchi, 1994; Takeuchi, 1995; Takeuchi, 2002)。6-8週齢時に、行動の停止に一致して脳波上7-8-Hzの棘徐波複合を特徴とする欠神様発作を示す(Tokuda, 2007)。遺伝解析の結果、gryはラット第19番染色体P/Q型電位依存性カルシウムチャネルCacna1aのミスセンス変異(M251K)であることが判明した(Tokuda, 2007)。ヒトの抗てんかん薬の一部がGRYの欠神様発作を抑えることが報告されている(Tokuda, 2007; Tokuda, 2010; Ohno, 2010)。(Oct 28, 20108) |
参考文献: |
Takeuchi IK, Takeuchi YK. Neuronal degeneration in the striatum of the groggy rat: a new mutant with a movement disorder. Experientia. 1991 Dec 1;47(11-12):1215-8.
Takeuchi IK, Aoki E, Takeuchi YK. Age-related and region-specific increase in number of concentric lamellar bodies in axon terminals and presynaptic axons in central nervous system of groggy mutant rat. Acta Neuropathol. 1994;87(6):628-34.
Takeuchi IK, Aoki E, Takeuchi YK. Axonal swellings in cerebellar white matter of groggy mutant rat. Acta Neuropathol. 1995;90(5):486-92.
Takeuchi IK, Aoki E, Takeuchi YK. Concentric lamellar bodies in axon terminals and preterminal axons of cerebellar Purkinje cells in groggy mutant rat: acid phosphatase cytochemistry. J Electron Microsc (Tokyo). 1995 Jun;44(3):140-4.
Takeuchi YK, Takeuchi IK. Neuronal degeneration in the septum of the groggy mutant rat. Gifu College Med. 2002, 18.
Tanaka K, Shirakawa H, Okada K, Konno M, Nakagawa T, Serikawa T, Kaneko S. Increased Ca2+ channel currents in cerebellar Purkinje cells of the ataxic groggy rat. Neurosci Lett. 2007 Oct 16;426(2):75-80.
Tokuda S, Kuramoto T, Tanaka K, Kaneko S, Takeuchi IK, Sasa M, Serikawa T. The ataxic groggy rat has a missense mutation in the P/Q-type voltage-gated Ca2+ channel alpha1A subunit gene and exhibits absence seizures. Brain Res. 2007 Feb 16;1133(1):168-77.
Tokuda S, Sofue N, Ohno Y, Sasa M, Serikawa T. Inhibitory effects of levetiracetam on absence seizures in a novel absence-like epilepsy animal model, Groggy rat. Brain Res. 2010 Nov 4;1359:298-303.
Ohno Y, Sofue N, Imaoku T, Morishita E, Kumafuji K, Sasa M, Serikawa T. Serotonergic modulation of absence-like seizures in groggy rats: a novel rat model of absence epilepsy. J Pharmacol Sci. 2010 Sep 16;114(1):99-105.
Kuramoto T, Nakanishi S, Ochiai M, Nakagama H, Voigt B, Serikawa T. Origins of Albino and Hooded Rats: Implications from Molecular Genetic Analysis across Modern Laboratory Rat Strains. PLoS One. 2012;7(8):e43059.
Yuya Harada, Yuki Nagao, Takahiro Mukai, Saki Shimizu, Kentaro Tokudome, Naofumi Kunisawa, Tadao Serikawa, Masashi Sasa, Yukihiro Ohno. Expressional Analysis of Inwardly Rectifying Kir4.1 Channels in Groggy Rats, a Rat Model of Absence Seizures. Archives of Neuroscience. 2014 october; 1(3): e18651
Serikawa T, Mashimo T, Kuramoto T, Voigt B, Ohno Y, Sasa M. Advances on Genetic Rat Models of Epilepsy. Exp Anim. 64(1):1-7, 2015. |