Table 4.
Mouse CoQ biosynthesis mutants
| Mouse Mutant | CoQ and CoQ Intermediates | Gross Phenotype |
|---|---|---|
| Spontaneous mutation | ||
| Pdss2kd/kd | Widespread moderate to severe CoQ deficiency | Nephrotic syndrome, kidney failure, impaired motor behavior, plasma lipid abnormalities, death by 9.5 mo of age |
| Germline mutation | ||
| Coq3+/− | Normal CoQ9 levels | Wild-type appearance, normal life span |
| Coq7+/− | Normal level of total CoQ9, mild CoQ9 loss in the IMM | Wild-type appearance, 30% longer life span |
| Coq8a/ADCK3−/− | Moderate CoQ9 loss in skeletal muscles, kidney, and liver, not in cerebellum and serum | Progressive cerebellar ataxia and mild exercise intolerance, normal life span |
| Coq9R239X | Global and severe CoQ9 loss | Poor overall growth, impaired motor function, progressive paralysis, death between 3 and 6 mo of age |
| Coq9Q95X | Moderate CoQ9 loss in the kidney and cerebrum, severe CoQ9 loss in skeletal muscle | Adult-onset mild myopathy |
| Conditional knockout | ||
| Pdss2 podocyte KO Nphs1-cre;Pdss2loxP/loxP | ND | Nephrotic syndrome |
| Pdss2 renal tubular epithelium KO PEPCK-cre;Pdss2loxP/loxP | ND | Absence of overt phenotype |
| Pdss2 Purkinje cell KO Pcp2-cre;Pdss2loxP/− | ND | Ataxia-like symptoms at 9.5 mo |
| Pdss2 Purkinje cell KO Pax2-cre;Pdss2 loxP/− | ND | Death within the first 36 h of life |
| Pdss2 liver KO Alb-cre;Pdss2 loxP/loxP | Severe CoQ9 loss in the liver | Absence of overt phenotype, altered amino acid and DNA metabolism |
| Pdss2 dopaminergic neuron KO DAT-cre;Pdss2loxP/loxP | ND | Loss of TH-positive neurons, motor deficit |
| Coq6 podocyte KO Nphs2-cre;Coq6loxP/loxP | Renal dysfunction, death at ≈10 mo | |
| Coq7 liver KO Alb-cre;Coq7 loxP/loxP | Severe CoQ9 loss and DMQ9 accumulation in the liver | Absence of overt phenotype, normal life span |
| Coq7 whole body inducible KO CAG-creERT2;Coq7 loxP/loxP | Global and severe CoQ9 loss and DMQ9 accumulation | Weight loss, loss of coat hair, kidney dysfunction, elevated blood lactate, short life span |
| Coq8a/ADCK3 Purkinje cell KO (Pcp2-Cre; Coq8aloxP/loxP) | ND | Ataxia |
| Coq8b/ADCK4 podocyte KO (Nphs2-Cre; Coq8bloxP/loxP) | ND | Renal disease, death at ≈12 mo |
IMM, inner mitochondrial membrane; KO, knockout; ND, not determined; TH, tyrosine hydroxylase. For references, see sect. 5.1.2.