Widespread non-central nervous system organ pathology in fragile X premutation carriers with fragile X-associated tremor/ataxia syndrome and CGG knock-in mice.
Widespread non-central nervous system organ pathology in fragile X premutation carriers with fragile X-associated tremor/ataxia syndrome and CGG knock-in mice.
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DOI：
10.1007/s00401-011-0860-9
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发表时间：
2011-10
影响因子：
12.7
通讯作者：
Hukema RK
中科院分区：
文献类型：
--
作者：
Hunsaker MR;Greco CM;Spath MA;Smits AP;Navarro CS;Tassone F;Kros JM;Severijnen LA;Berry-Kravis EM;Berman RF;Hagerman PJ;Willemsen R;Hagerman RJ;Hukema RK
脆性 X 相关震颤/共济失调综合征 (FXTAS) 是一种成人发病的神经退行性疾病，通常表现为意向性震颤和步态共济失调，但伴有越来越多的合并症，包括甲状腺功能减退、高血压、周围神经病变和认知能力下降。 FXTAS 的病理特征是神经元和星形胶质细胞中均存在核内包涵体。然而，尚不清楚此类内含物在中枢神经系统（CNS）之外的存在程度。为了解决这个问题，我们使用 FXTAS 和已知具有神经元和星形胶质细胞内含物的 CGG 重复敲入 (CGG KI) 小鼠模型调查了 10 例人类病例的非中枢神经系统器官。我们在 FXTAS 病例和 CGG KI 小鼠的多个组织中发现了内含物，包括胰腺、甲状腺、肾上腺、胃肠道、垂体、松果体、心脏和二尖瓣，以及整个相关的自主神经节。在 FXTAS 病例的睾丸、附睾和肾脏中观察到包涵体，但在小鼠中未观察到。这些观察结果表明周围神经系统和全身器官的广泛参与。在 FXTAS 病例以及 CGG KI 小鼠的非 CNS 体器官系统、整个 PNS 和肠神经系统中发现核内包涵体，表明这些组织可能作为评估早期干预策略的潜在位点或用作诊断因素。
Fragile X-associated tremor/ataxia syndrome (FXTAS) is an adult-onset neurodegenerative disorder generally presenting with intention tremor and gait ataxia, but with a growing list of co-morbid medical conditions including hypothyroidism, hypertension, peripheral neuropathy, and cognitive decline. The pathological hallmark of FXTAS is the presence of intranuclear inclusions in both neurons and astroglia. However, it is unknown to what extent such inclusions are present outside the central nervous system (CNS). To address this issue, we surveyed non-CNS organs in ten human cases with FXTAS and in a CGG repeat knock-in (CGG KI) mouse model known to possess neuronal and astroglial inclusions. We find inclusions in multiple tissues from FXTAS cases and CGG KI mice, including pancreas, thyroid, adrenal gland, gastrointestinal, pituitary gland, pineal gland, heart, and mitral valve, as well as throughout the associated autonomic ganglia. Inclusions were observed in the testes, epididymis, and kidney of FXTAS cases, but were not observed in mice. These observations demonstrate extensive involvement of the peripheral nervous system and systemic organs. The finding of intranuclear inclusions in non-CNS somaticorgan systems, throughout the PNS, and in the enteric nervous system of both FXTAS cases as well as CGG KI mice suggests that these tissues may serve as potential sites to evaluate early intervention strategies or be used as diagnostic factors.
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DOI：
10.4088/jcp.08m04476
发表时间：
2009-06
期刊：
The Journal of clinical psychiatry
影响因子：
--
作者：
Bourgeois JA;Coffey SM;Rivera SM;Hessl D;Gane LW;Tassone F;Greco C;Finucane B;Nelson L;Berry-Kravis E;Grigsby J;Hagerman PJ;Hagerman RJ
通讯作者：
Hagerman RJ
DOI：
10.2310/jim.0b013e3181af59d6
发表时间：
2009-12
期刊：
Journal of investigative medicine : the official publication of the American Federation for Clinical Research
影响因子：
--
作者：
Berman RF;Willemsen R
通讯作者：
Willemsen R
影响因子：
2
作者：
Berry-Kravis, Elizabeth;Goetz, Christopher G.;Hagerman, Paul J.
通讯作者：
Hagerman, Paul J.
影响因子：
2.3
作者：
Gokden, Murat;Al-Hinti, Jomana T.;Harik, Sami I.
通讯作者：
Harik, Sami I.
DOI：
10.1002/ajmg.b.30910
发表时间：
2009-09-05
影响因子：
2.8
作者：
Brouwer, J. R.;Willemsen, R.;Oostra, B. A.
通讯作者：
Oostra, B. A.