Arginine:glycine amidinotransferase‐ and guanidinoacetate methyltransferase deficiency are severe neurodevelopmental disorders. It is not known whether mouse models of disease express a neuroanatomical phenotype. High‐resolution magnetic resonance imaging (MRI) with advanced image analysis was performed in perfused, fixed mouse brains encapsulated with the skull from male, 10‐12 week old Agat ^‐exc and B6J.Cg‐Gamt ^tm1Isb mice (n = 48; n = 8 per genotype, strain). T2‐weighted MRI scans were nonlinearly aligned to a 3D atlas of the mouse brain with 62 structures identified. Local differences in brain shape related to genotype were assessed by analysis of deformation fields. Creatine (Cr) and guanidinoacetate (GAA) were measured with high‐performance liquid chromatography (HPLC) in brain homogenates (n = 24; n = 4 per genotype, strain) after whole‐body perfusion. Cr was decreased in the brain of Agat‐ and Gamt mutant mice. GAA was decreased in Agat^−/− and increased in Gamt^−/−. Body weight and brain volume were lower in Agat^−/− than in Gamt^−/−. The analysis of entire brain structures revealed corpus callosum, internal capsule, fimbria and hypothalamus being different between the genotypes in both strains. Eighteen and fourteen significant peaks (local areas of difference in relative size) were found in Agat‐ and Gamt mutants, respectively. Comparing Agat^−/− with Gamt^−/−, we found changes in three brain regions, lateral septum, amygdala, and medulla. Intra‐strain differences in four brain structures can be associated with Cr deficiency, while the inter‐strain differences in three brain structures of the mutant mice may relate to GAA. Correlating these neuroanatomical findings with gene expression data implies the role of Cr metabolism in the developing brain and the importance of early intervention in patients with Cr deficiency syndromes.

中文翻译：

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磁共振成像揭示了 Agat 和 Gamt 小鼠大脑中由肌酸消耗和胍基乙酸盐改变引起的特定解剖学变化。

精氨酸：甘氨酸脒基转移酶和胍基乙酸甲基转移酶缺乏是严重的神经发育障碍。尚不清楚疾病的小鼠模型是否表达神经解剖学表型。高分辨率磁共振成像（MRI）与高级图像分析是在封装有从雄性，10-12周龄颅骨灌注，固定小鼠脑进行阿加特^-EXC和B6J.Cg-GAMT ^tm1Isb 小鼠（n = 48；每个基因型、品系 n = 8）。T2 加权 MRI 扫描与小鼠大脑的 3D 图谱非线性对齐，其中确定了 62 个结构。通过分析变形场来评估与基因型相关的大脑形状的局部差异。全身灌注后，用高效液相色谱 (HPLC) 测量脑匀浆（n = 24；每个基因型、菌株 n = 4）中的肌酸 (Cr) 和胍基乙酸盐 (GAA)。Agat- 和 Gamt 突变小鼠大脑中的 Cr 降低。GAA 在 Agat ^-/-中减少，在 Gamt ^{-/- 中}增加。Agat ^{-/- 的}体重和脑容量低于Gamt ^-/-. 对整个大脑结构的分析表明，两种菌株的基因型之间的胼胝体、内囊、菌毛和下丘脑是不同的。在 Agat- 和 Gamt 突变体中分别发现了 18 个和 14 个显着峰（相对大小差异的局部区域）。比较 Agat ^−/−与 Gamt ^−/−，我们发现了三个大脑区域的变化，即侧隔、杏仁核和髓质。四种脑结构的品系间差异可能与 Cr 缺乏有关，而突变小鼠三种大脑结构的品系间差异可能与 GAA 相关。将这些神经解剖学发现与基因表达数据相关联，暗示了 Cr 代谢在发育中的大脑中的作用以及对 Cr 缺乏综合征患者进行早期干预的重要性。