Behavioural Characterisation of Macrod1 and Macrod2 Knockout Mice.
Behavioural Characterisation of Macrod1 and Macrod2 Knockout Mice.
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作者：
Crawford K;Oliver PL;Agnew T;Hunn BHM;Ahel I
腺苷二磷酸核糖基化（ADP-ribosylation; ADPr）是一种高度保守的修饰，涉及广泛的细胞功能，从病毒防御、DNA损伤反应（DDR）、代谢、致癌和神经生物学。在这里，我们研究MACROD 1和MACROD 2（单ADP-核糖基水解酶1和2），两个最不了解ADPr-单水解酶。据报道，MACROD 1主要定位于线粒体，而MACROD 2基因组位点与各种神经系统疾病如自闭症、注意缺陷多动障碍（ADHD）和精神分裂症有关;但在哺乳动物行为背景下破坏这些蛋白质的潜在意义尚不清楚。因此，在这里，我们分析了Macrod 1和Macrod 2基因敲除（KO）小鼠模型在电池的定义明确，自发的行为测试范例。Macrod 1的缺失导致女性特有的运动协调缺陷，而Macrod 2的破坏与随着年龄增长而变得更加明显的多动相关，并与运动迟缓样步态相结合。这些数据揭示了ADPr-单水解酶在与线粒体和神经精神疾病相关的行为方面的重要性的新见解。
Adenosine diphosphate ribosylation (ADP-ribosylation; ADPr), the addition of ADP-ribose moieties onto proteins and nucleic acids, is a highly conserved modification involved in a wide range of cellular functions, from viral defence, DNA damage response (DDR), metabolism, carcinogenesis and neurobiology. Here we study MACROD1 and MACROD2 (mono-ADP-ribosylhydrolases 1 and 2), two of the least well-understood ADPr-mono-hydrolases. MACROD1 has been reported to be largely localized to the mitochondria, while the MACROD2 genomic locus has been associated with various neurological conditions such as autism, attention deficit hyperactivity disorder (ADHD) and schizophrenia; yet the potential significance of disrupting these proteins in the context of mammalian behaviour is unknown. Therefore, here we analysed both Macrod1 and Macrod2 gene knockout (KO) mouse models in a battery of well-defined, spontaneous behavioural testing paradigms. Loss of Macrod1 resulted in a female-specific motor-coordination defect, whereas Macrod2 disruption was associated with hyperactivity that became more pronounced with age, in combination with a bradykinesia-like gait. These data reveal new insights into the importance of ADPr-mono-hydrolases in aspects of behaviour associated with both mitochondrial and neuropsychiatric disorders.
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影响因子：
29
作者：
Civiletto G;Varanita T;Cerutti R;Gorletta T;Barbaro S;Marchet S;Lamperti C;Viscomi C;Scorrano L;Zeviani M
通讯作者：
Zeviani M
影响因子：
3.4
作者：
Andrabi, Syed Suhail;Tabassum, Heena;Parvez, Suhel
通讯作者：
Parvez, Suhel
影响因子：
64.8
作者：
Dickinson ME;Flenniken AM;Ji X;Teboul L;Wong MD;White JK;Meehan TF;Weninger WJ;Westerberg H;Adissu H;Baker CN;Bower L;Brown JM;Caddle LB;Chiani F;Clary D;Cleak J;Daly MJ;Denegre JM;Doe B;Dolan ME;Edie SM;Fuchs H;Gailus-Durner V;Galli A;Gambadoro A;Gallegos J;Guo S;Horner NR;Hsu CW;Johnson SJ;Kalaga S;Keith LC;Lanoue L;Lawson TN;Lek M;Mark M;Marschall S;Mason J;McElwee ML;Newbigging S;Nutter LM;Peterson KA;Ramirez-Solis R;Rowland DJ;Ryder E;Samocha KE;Seavitt JR;Selloum M;Szoke-Kovacs Z;Tamura M;Trainor AG;Tudose I;Wakana S;Warren J;Wendling O;West DB;Wong L;Yoshiki A;International Mouse Phenotyping Consortium;Jackson Laboratory;Infrastructure Nationale PHENOMIN, Institut Clinique de la Souris (ICS);Charles River Laboratories;MRC Harwell;Toronto Centre for Phenogenomics;Wellcome Trust Sanger Institute;RIKEN BioResource Center;MacArthur DG;Tocchini-Valentini GP;Gao X;Flicek P;Bradley A;Skarnes WC;Justice MJ;Parkinson HE;Moore M;Wells S;Braun RE;Svenson KL;de Angelis MH;Herault Y;Mohun T;Mallon AM;Henkelman RM;Brown SD;Adams DJ;Lloyd KC;McKerlie C;Beaudet AL;Bućan M;Murray SA
通讯作者：
Murray SA
影响因子：
3.7
作者：
Delwig, Anton;Logan, Anne M.;Ahn, Andrew H.
通讯作者：
Ahn, Andrew H.
DOI：
10.1073/pnas.0808312105
发表时间：
2008-12-16
影响因子：
11.1
作者：
Altimus, C. M.;Guler, A. D.;Hattar, S.
通讯作者：
Hattar, S.