Zebrafish inversin mutants develop scoliosis in the absence of laterality defects.

BACKGROUND

Human mutations in INVERSIN are associated with nephronophthisis, variable penetrance of situs inversus and congenital heart disease. Inversin has been shown to localize to cilia and many of the patient phenotypes are attributed to disrupted cilia function. We set out to characterize the invssa12246 allele in zebrafish to investigate its utility in understanding patient disease.

RESULTS

The left-right axis is established correctly in invssa12246 mutants, kidneys appear to develop normally without any cysts and cilia appear normal, however mutants are significantly shorter. In post-embryonic stages, invssa12246 mutants display significant growth delay and signs of retinal mis-patterning together with spinal deformities reminiscent of idiopathic scoliosis. The allele is lethal in the juvenile stage.

CONCLUSIONS

We show that invssa12246 allele has a distinct phenotype from other models where inversin function is disrupted, uncovering novel roles in post-embryonic development.