Table 3.
Main characteristics of the different GSD mouse models. Abbreviations. ALP: alkaline phosphatase, ALT: alanine transaminase, AST: aspartate transaminase, CPK: creatine phosphokinase, diaph: diaphragm, f.i: fold increase, HCA: hepatocellular adenoma, N.A: not applicable, Skm: skeletal muscle.
| Glycogenosis | Model | Major Organs Affected | Growth Impairment | Blood Analyses | Glycogen Content | Impaired Exercise Capacity | Premature Death | % of Premature Death/Cause | References |
|---|---|---|---|---|---|---|---|---|---|
| 0b | Gys1-/- | Heart | Yes | Hypolactatemia | Absence (skeletal muscle, heart) | Endurance (fasting) | Yes/perinatal | ~90%/abnormal cardiac development | [106,107,108] |
| Ia | G6pc-/- | Liver, kidney | Yes | Hypoglycemia, hyperlipidemia, hyperuricemia | Increased (~20 and ~30 f.i in liver and kidney, respectively) | Not reported | Yes/~weaning | ~90%/hypoglycemia | [112,117,118,119,120,121,122,123,124,125,126,127] |
| L-G6pc-/- | Liver | No | Hypertriglyceridemia, hyperuricemia, hypercholesterolemia, hyperlactacidemia | Increased (~2–2.5 f.i in liver) | Not reported | No | N.A. | [128] | |
| K-G6pc-/- | Kidney | No | Hyperuricemia | Increased (~22 f.i in kidney) | Not reported | No | N.A. | [129] | |
| I-G6pc-/- | Intestine | No | None reported | None reported | Not reported | No | N.A. | [130] | |
| Ib | Slc37a4-/- | Liver, kidney, bone marrow, spleen | Yes | Hypoglicemia, hyperlipidemia, hyperuricemia, hyperlactacidemia, neutropenia, leucopenia | Increased (liver, kidney) | Not reported | Yes/~weaning | ~90%/hypoglycemia | [131,132,133,134] |
| TM-Slc37a4-/- | Liver, kidney, bone marrow, spleen | No | Hypertriglyceridemia, hypercholesterolemia, hyperalbuminemia, neutropenia, Increased AST | Increased (~6.5 and ~2.5–5 f.i in kidney and liver, respectively) | Not reported | No | N.A. | [135] | |
| II | 6neo/6neo | Skm, heart, diaph | No | Not reported | Increased (~45, 17, 16 f.i in heart, quad and gast, respectively). Also in diaph | Yes | No | N.A. | [146,147,148,149,150,151,152,153,154,155,156,157,158,159,160,161,162,163,164,165,166,167,168,169,170,171,172,173,174,175,176,177,178,179,180,181,182] |
| AD-6neo/6neo | Skm, heart, diaph | Yes | Not reported | Increased (~45, 11, 10 f.i in heart, quad and gast, respectively). Also in diaph | Yes | Yes | Not reported/respiratory failure | [183,184] | |
| AD2-6neo/6neo | Skm, heart, diaph | Not reported | Not reported | Increased (~45, 8, 5.5 f.i in heart, quad and gast, respectively). Also in diaph | Not reported | Not reported | Not reported | [185] | |
| Δ6/Δ6 | Skm, heart, diaph | No | Not reported | Increased (~360 and ~42 f.i in diaph and skm, respectively). Also in heart and brain | No | No | N.A. | [146,150] | |
| 13neo/13neo | Skm, heart | No | Not reported | Increased (skeletal muscle, heart) | Not reported | No | N.A. | [186] | |
| Δ14neo/Δ14neo | Skm, heart, brain | No | Not reported | Increased (~320 and ~41 f.i in diaph and skm, respectively). Also in heart and brain | Yes | No | N.A. | [150] | |
| Gaa KODBA | Skm, heart, diaph | No | Not reported | Increased (skm, heart diaph) | Yes | Yes/within first 6 months | ~50%/respiratory failure | [151] | |
| Gaac.1826dupA | Skm, heart, diaph | Yes | Not reported | Increased (~185 and ~28 f.i. in heart and gast, respectively) | Yes | No | N.A. | [183] | |
| III | AglEX5-/- | Liver, Skm, heart | No | Hypoglycemia, Increased AST, ALT, ALP and CPK | Increased (~200, ~50, ~25, ~22 f.i in liver, diaph, heart and gast, respectively) | Yes | No | N.A. | [49] |
| AglEX32-/- | Liver, Skm, heart | No | Hypoglycemia, Increased ALT, AST, ALP | Increased (~26, ~22, ~2.5 f.i. in heart, skm, liver respectively) | Yes | Yes/within first year | Unknown | [194] | |
| AglEX6-10-/- | Liver, Skm, heart, brain | No | Hypoglycemia | Increased (~8, ~3, ~3 f.i. in skm, liver, heart, respectively) | Yes | No | N.A. | [195] | |
| AglEX6-10-/- 2 | Liver, Skm, heart, brain | No | Increased ALT | Increased (~150, ~50, ~30 f.i. in liver, skm, heart respectively) | Yes | No | N.A. | [196] | |
| IV | Gbe1neo/neo | Liver, Skm, heart, brain | No | Hypoglycemia (slight) | Increased (liver, skm) | Not reported | Yes/within first 11 months | ~100%/unknown | [199] |
| Gbe1-/- | Liver, Skm, heart | N.A | None reported | Reduced (skm) | Not reported | Yes/soon after birth | ~100%/unknown | [199] | |
| Gbe1ys/ys | Liver, Skm, heart, brain | No | Hypoglycemia (slight), hyperCKemia, increased ALT and AST | Increased (~90, ~32, ~17, ~1.5, heart, skm, brain and liver, respectively | Yes | Yes/before 20 months | ~100%/unknown | [200,201] | |
| V | PygmR50X/R50X | Skm | No | HyperCKemia, hyperammonemia, Hypolactatemia, hypoglycemia | Increased (~40, ~20 and ~15 f.i in TA, quad and gast, respectively) | Yes | Yes/perinatal and post-weaning | ~85%/unknown | [208,209,210,211,212,213,214] |
| VI | Pygl-/- | Liver | No | Hypoglycemia, hyperketonemia, increased ALT and AST | Increased (~60 f.i in liver) | Not reported | No | N.A. | [216] |
| VII | Pfkm-/- | Skm, heart, diaph, spleen | No | Hypolactatemia, hyperbilirubinemia | Increased (~8 f.i in diaph). Also increased in skm and heart | Yes | Yes/around weaning | 60%/unknown | [227] |
| XV | Gyg-/- | Skm | No | Not reported | Increased (7 and 4 f.i. in heart and skm) | Decreased aerobic, increased anaerobic | Yes/perinatal | ~85%/cardio-respiratory failure | [228] |