| First Author | Haaning AM | Year | 2013 |
| Journal | Pediatr Res | Volume | 74 |
| Issue | 5 | Pages | 494-502 |
| PubMed ID | 23999067 | Mgi Jnum | J:317602 |
| Mgi Id | MGI:6855345 | Doi | 10.1038/pr.2013.147 |
| Citation | Haaning AM, et al. (2013) Heterotaxy-spectrum heart defects in Zic3 hypomorphic mice. Pediatr Res 74(5):494-502 |
| abstractText | BACKGROUND: Mutations in Zinc Finger Protein of the Cerebellum 3 (ZIC3) cause X-linked heterotaxy and isolated cardiovascular malformations. Recent data suggest a potential cell-autonomous role for Zic3 in myocardium via regulation of Nppa and Tbx5. We sought to develop a hypomorphic Zic3 mouse to model human heterotaxy and investigate developmental mechanisms underlying variability in cardiac phenotypes. METHODS: Zic3 hypomorphic mice were created by targeted insertion of a neomycin cassette and investigated by gross, histologic, and molecular methods. RESULTS: Low-level Zic3 expression is sufficient for partial rescue of viability as compared with Zic3 null mice. Concordance of early left-right molecular marker abnormalities and later anatomic abnormalities suggests that the primary effect of Zic3 in heart development occurs during left-right patterning. Cardiac-specific gene expression of Nppa (atrial natriuretic factor) and Tbx5 marked the proper morphological locations in the heart regardless of looping abnormalities. CONCLUSION: Zic3 hypomorphic mice are useful models to investigate the variable cardiac defects resulting from a single genetic defect. Low-level Zic3 expression rescues the left pulmonary isomerism identified in Zic3 null embryos. Our data do not support a direct role for Zic3 in the myocardium via regulation of Nppa and Tbx5 and suggest that the primary effect of Zic3 on cardiac development occurs during left-right patterning. |
