Intellectual Disability and Brain Creatine Deficit: Phenotyping of the Genetic Mouse Model for GAMT Deficiency

Genes

Mauro Magnani¹  Francesca Pierigè¹  Luigia Rossi¹  Claudia Carducci²  Tiziana Pascucci³  Rossella Ventura³  Simona Cabib³  Vincenzo Leuzzi⁴  Francesca Nardecchia⁴ 

[1] Department of Biomolecular Sciences, University of Urbino “Carlo Bo”, 61029 Urbino, Italy;Department of Experimental Medicine, Sapienza University, 00161 Rome, Italy;Department of Psychology and “Daniel Bovet” Center, Sapienza University, 00184 Rome, Italy;Division of Child Neurology and Psychiatry, Department of Human Neuroscience, Sapienza University, 00185 Rome, Italy;

关键词: GAMT deficiency;    genetic mouse model;    behavioral phenotyping;    developmental delay;   

DOI  :  10.3390/genes12081201

来源: DOAJ

【 摘 要 】

Guanidinoacetate methyltransferase deficiency (GAMT-D) is one of three cerebral creatine (Cr) deficiency syndromes due to pathogenic variants in the GAMT gene (19p13.3). GAMT-D is characterized by the accumulation of guanidinoacetic acid (GAA) and the depletion of Cr, which result in severe global developmental delay (and intellectual disability), movement disorder, and epilepsy. The GAMT knockout (KO) mouse model presents biochemical alterations in bodily fluids, the brain, and muscles, including increased GAA and decreased Cr and creatinine (Crn) levels, which are similar to those observed in humans. At the behavioral level, only limited and mild alterations have been reported, with a large part of analyzed behaviors being unaffected in GAMT KO as compared with wild-type mice. At the cerebral level, decreased Cr and Crn and increased GAA and other guanidine compound levels have been observed. Nevertheless, the effects of Cr deficiency and GAA accumulation on many neurochemical, morphological, and molecular processes have not yet been explored. In this review, we summarize data regarding behavioral and cerebral GAMT KO phenotypes, and focus on uncharted behavioral alterations that are comparable with the clinical symptoms reported in GAMT-D patients, including intellectual disability, poor speech, and autistic-like behaviors, as well as unexplored Cr-induced cerebral alterations.

【 授权许可】

Unknown