Table 1.
Phenotypes of Animals With Mutations in Genes Critical for Copper Homeostasis During Development
| Gene | Functions | Phenotypes | Reference |
|---|---|---|---|
| Atox1 | Copper chaperone for ATP7A/B | Perinatal lethal, severe growth retardation in null mouse | (Hamza et al., 2001) |
| Atp7a | Copper transporter into TGN | Fatal in early childhood in MNK disease | (Mercer, 1998) |
| Embryonic lethal, perinatal lethal or hypopigmentation in mottled/brindled mouse | (Mercer, 1998) | ||
| Impaired synaptogenesis and axonal targeting, cytoskeletal dysfunction in mottled/brindled mouse | (El Meskini et al., 2007; Niciu et al., 2007) | ||
| Impaired notochord development in calamity zebrafish | (Mendelsohn et al., 2006) | ||
| Impaired early larval development and adult pigmentation in Drosophila | (Norgate et al., 2006) | ||
| Atp7b | Copper transporter into TGN | Abnormal copper accumulation in the liver and CNS in WND patients | (Van Hoof et al., 1992) |
| Abnormal copper accumulation in the liver of Long–Evans Cinnamon rat | (Muramatsu et al., 1994) | ||
| Copper deficiency in breast milk in toxic milk and null mouse | (Buiakova et al., 1999) | ||
| Commd1 | Ubiquitin pathway regulation | Copper toxicosis in Bedlington terrier | (van de Sluis et al., 2002) |
| ATP7B stability | Embryonic lethal (E9.5–E10.5) in null mouse, no placental vascularization | (van de Sluis et al., 2007) | |
| Cox17 | Copper chaperone for CCO | Embryonic lethal (E8.5–E10) in null mouse | (Takahashi et al., 2002) |
| Ctr1 | Copper importer (cell signaling?) | Embryonic lethal (E8.5–E10.5) in null mouse | (Kuo et al., 2001; Lee et al., 2001) |
| Impaired development of neuroectoderm and mesoderm arrest at larval stage in Drosophila | (Turski and Thiele, 2007) | ||
| Sco1/2 | Copper chaperone for CCO | Fatal infantile cardioencephalomyopathy and CCO deficiency (Sco2) in humans | (Papadopoulou et al., 1999) |
| Neonatal liver failure and encephalopathy (Sco1) in humans | (Valnot et al., 2000) |