Intellectual Disability and Brain Creatine Deficit: Phenotyping of the Genetic Mouse Model for GAMT Deficiency
Abstract
:1. Introduction
2. GAMT-D Syndrome: Clinical and Biochemical Profiling
3. GAMT KO Mouse Model
3.1. Biochemical Profiling
3.1.1. Bodily Fluids
3.1.2. Skeletal Muscle
3.1.3. Brain
3.2. Behavioral Profiling
3.2.1. Early Postnatal Behavioral Development
3.2.2. Neuromuscular Disorder
3.2.3. Learning and Memory Tasks
3.2.4. Social Behavior Tasks
4. Discussion
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Tissue | Compound | Genotype | |||||||
---|---|---|---|---|---|---|---|---|---|
WT | HZ | KO | |||||||
Urine (nmol/24 h) | Cr | 13,490 ± 3967 | 8394 ± 2739 | 20,883 ± 7603 | 5130 ± 1373 | 5672 ± 1203 | 71 ± 56 ** | 47 ± 36 *** | 4144 ± 1496 |
Crn | 9188 ± 1753 | 6491 ± 1336 | 54.8 ± 12 | 6991 ± 853 | 6206 ± 926 | 1153 ± 268 *** | 536 ± 124 *** | 55.6 ± 19.8 | |
GAA | 3005 ± 880 | 2023 ± 575 | 320 ± 37 | 2335 ± 538 | 2065 ± 522 | 25,775 ± 2867 *** | 19,015 ± 2887 *** | 372 ± 27.4 | |
Plasma or Serum (µmol/L) | Cr | 172.4 ± 16.4 | 172 ± 16 | 1347 ± 205 | 187 ± 32.7 | 190 ± 24 | 12.9 ± 8.1 *** | 11.56 ± 7.1 *** | 822 ± 416 |
Crn | 8.9 ± 0.8 | 8.89 ± 0.73 | 5.5 ± 0.8 | 9.4 ± 0.6 | 9.50 ± 0.94 | 1.3 ± 0.3 *** | <0.4–2.15 ° | 1 ± 0.2 | |
GAA | 1.9 ± 0.5 | 1.94 ± 0.41 | 33.3 ± 14.6 | 2.4 ± 0.3 | 1.97 ± 0.37 | 117.4 ± 32.1 ** | 106 ± 29 * | 97.6 ± 7.8 | |
Reference | [39] A | [5] B | [40] C | [39] A | [5] B | [39] A | [5] B | [40] C |
Tissue | Compound | Genotype | |||||
---|---|---|---|---|---|---|---|
WT | KO | ||||||
Muscle (mM) | Cr | 28.4 ± 2.6 | 17.5 ± 0.3 | 27.7 ± 3.9 | 8.9 ± 3.8 | 1.6 ± 0.3 *** | 3.4 ± 3.9 * |
GAA | - | 0.002 ± 0.0005 | - | - | 15.3 ± 2.2 *** | - | |
Reference | [38] A | [5] B | [44] C | [38] A | [5] B | [44] C |
Tissue | Compound | Genotype | |||
---|---|---|---|---|---|
WT | KO | ||||
Muscle (phosphate ratios) | PCR/ATP | 2.66 ± 0.11 | 3.16 ± 0.10 | 0.76 ± 0.33 | N.D. |
PGAA/ATP | N.D. | N.D. | 1.78 ± 0.42 | 3.04 ± 0.06 | |
Muscle (mM) | PCR | 18.86 ± 0.78 | 22.40 ± 0.71 | 3.83 ± 1.66 | N.D. |
PGAA | N.D. | N.D. | 8.97 ± 2.01 | 15.32 ± 0.30 | |
Reference | [38] | [43] | [38] | [43] |
Tissue | Compound | Genotype | |||||||
---|---|---|---|---|---|---|---|---|---|
WT | HZ | KO | |||||||
Brain (mM) | Cr | 10.752 ± 1.15 | 11.841 ± 0.44 | 8.2 ± 1.2 | 11.005 ± 0.439 | 10.853 ± 0.488 | 0.454 ± 0.097 | 0.489 ± 0.09 *** | 1.4 ± 0.4 |
Crn | 0.356 ± 0.04 | 0.339 ± 0.50 | 0.186 ± 0.049 | 0.258 ± 0.040 | 0.00945 ± 0.00004 | <DL-0.02121 ° | |||
GAA | 0.0123 ± 0.002 | 0.0128 ± 1.37 | 0.0148 ± 0.001 | 0.0134 ± 0.001 | 1.958 ± 0.070 | 1.945 ± 0.064 *** | 1.3 ^ | ||
Reference | [39] A | [5] B | [38] C | [39] A | [5] B | [39] A | [5] B | [38] C |
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Rossi, L.; Nardecchia, F.; Pierigè, F.; Ventura, R.; Carducci, C.; Leuzzi, V.; Magnani, M.; Cabib, S.; Pascucci, T. Intellectual Disability and Brain Creatine Deficit: Phenotyping of the Genetic Mouse Model for GAMT Deficiency. Genes 2021, 12, 1201. https://doi.org/10.3390/genes12081201
Rossi L, Nardecchia F, Pierigè F, Ventura R, Carducci C, Leuzzi V, Magnani M, Cabib S, Pascucci T. Intellectual Disability and Brain Creatine Deficit: Phenotyping of the Genetic Mouse Model for GAMT Deficiency. Genes. 2021; 12(8):1201. https://doi.org/10.3390/genes12081201
Chicago/Turabian StyleRossi, Luigia, Francesca Nardecchia, Francesca Pierigè, Rossella Ventura, Claudia Carducci, Vincenzo Leuzzi, Mauro Magnani, Simona Cabib, and Tiziana Pascucci. 2021. "Intellectual Disability and Brain Creatine Deficit: Phenotyping of the Genetic Mouse Model for GAMT Deficiency" Genes 12, no. 8: 1201. https://doi.org/10.3390/genes12081201
APA StyleRossi, L., Nardecchia, F., Pierigè, F., Ventura, R., Carducci, C., Leuzzi, V., Magnani, M., Cabib, S., & Pascucci, T. (2021). Intellectual Disability and Brain Creatine Deficit: Phenotyping of the Genetic Mouse Model for GAMT Deficiency. Genes, 12(8), 1201. https://doi.org/10.3390/genes12081201