A new rat model of creatine transporter deficiency reveals behavioral disorder and altered brain metabolism

• DOI: 10.1038/s41598-020-80824-x
• Publication Date: 2021-01-15T11:02:30Z
• Authors: Lara Duran-Trio; Gabriella Fernand...; Dunja Simicic; Jocelyn Grosse; Clothilde Roux-Pe...; Stephen J. Bruce; Pierre-Alain Binz; Carmen Sandi; Cristina Cudalbu; Olivier Braissant
• Keywords: Creatine; Creatine Monohydrate

Abstract Creatine is an organic compound used as fast phosphate energy buffer to recycle ATP, important in tissues with high demand such muscle or brain. taken from the diet endogenously synthetized by enzymes AGAT and GAMT, specifically up transporter SLC6A8. Deficit endogenous synthesis transport leads Cerebral Deficiency Syndromes (CCDS). CCDS are characterized brain creatine deficiency, intellectual disability severe speech delay, behavioral troubles attention deficits and/or autistic features, epilepsy. Among CCDS, X-linked deficiency (CTD) most prevalent no efficient treatment so far. Different mouse models of CTD were generated doing long deletions Slc6a8 gene showing reduced cognitive deficiencies impaired motor function. We present a new knock-in (KI) rat model holding identical point mutation found patients reported lack activity. KI males showed increased urinary creatine/creatinine ratio, autistic-like traits. The Y389C fairly enriches spectrum provides data about pathology, being first animal carrying mutation.