Development of the membranous labyrinth in E9.5 to E14.5 C57BL/6N mouse embryos. Stage specific metric and descriptive reference data and their use for identifying malformations.

Morphological phenotyping of genetically engineered or experimentally challenged mice is the first step in researching the causality of congenital malformations. Especially for spatially complex structures like the inner ear, this is challenging. Our study aims at providing detailed anatomic descriptions and metric information on the membranous labyrinth of mouse embryos from the first demarcation of the otic vesicle to the transition to fetal life. It further intends to use these data as references for objective characterizations of abnormalities in embryos of knock out lines. Using digital data produced from C57BL/6 wild type mouse embryos, 218 surface models of membranous labyrinths were generated and analyzed. The embryo data had been created in the "Deciphering the mechanisms of developmental disorders" program with the aid of "High-resolution episcopic microscopy" and had been staged according to Theiler and Geyer. Detailed anatomic descriptions and measurements of the angles between planes through the semicircular canals and coils of the cochlear duct and the sagittal and horizontal planes as well as measurements of the volumina of the membranous labyrinth and its vestibular, cochlear and endolymphatic components are provided for each developmental stage. This objective metric information was used for diagnosing malformations of the membranous labyrinth of embryos of eight knock-out lines. Our study provides novel information on the normal development of the membranous labyrinth of C57BL/6 embryos, reference data for detailed, objective and stage specific phenotyping of mutants and first results of employing the data for characterizing the spectrum of inner ear malformations in genetically engineered embryos.