| 67547 |
Q91W10 |
S39A8_MOUSE |
Metal cation symporter ZIP8 (Solute carrier family 39 member 8) (Zrt- and Irt-like protein 8) (ZIP-8) |
DISRUPTION PHENOTYPE |
The homozygous knockout of Slc39a8 is embryonic lethal by 16.5 dpc. Hearts exhibit hypertrabeculation and non-compaction phenotypes including excessive trabeculae and thin compact myocardium. These phenotypes are evident at 12.5 dpc and prominent at 14.5 dpc, and embryos that survive until 16.5 dpc display an even stronger phenotype. Ventricular septal defects are also observed. Some 14.5 dpc embryos exhibit body edema, suggesting that cardiac muscle function is compromised. Hearts display increased cardiomyocyte proliferation (PubMed:29337306). This is associated with decreased expression of metalloproteases and impaired degradation of the extracellular matrix leading to its aberrant accumulation in heart (PubMed:29337306). In mice homozygous for an hypomorphic allele of the gene, resulting in significant decreased expression of the protein, hematopoiesis and the development of multiple organs are affected from very early embryogenesis (PubMed:22563477). Conditional knockout of the gene at the level of the whole organism decreases manganese levels in tissues but has no effect on zinc and iron (PubMed:28481222). Conditional liver-specific knockout of the gene results in decreased systemic tissue manganese levels coupled to increased manganese in bile but has no effect on zinc or iron levels (PubMed:28481222). {ECO:0000269|PubMed:22563477, ECO:0000269|PubMed:28481222, ECO:0000269|PubMed:29337306}. |