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Induced and genetic mouse middle ear ossicular malformations: a model for human malformative ossicular diseases and a tool for clarifying their normal ontogenesis

Malformations des osselets de l'ouïe de la souris d'origine génétique et induite : un modèle pour les malformations ossiculaires humaines et une aide pour la compréhension de leur ontogenèse normale

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Summary

Oral administration of 13-cis retinoic acid (RA) to pregnant mice on the 9th gestation day provokes important malformations of the middle ear ossicles, associated with a general kind of craniofacial dysmorphogenesis evoking the human mandibulofacial dysostosis. The malleus, incus and stapes are affected. The malleus exhibits a handle separated from its head and keeping a persistant relationship with the tubotympanic recess. The stapes makes no contact with the otic capsule. The malformation pattern is visible early as shown by the appearance of an abnormally curved Meckel's cartilage at day 12, followed by the development of atypically shaped ossicular anlagen. The mouse “far” (first arch malformation) mutation is responsible for minor ossicular abnormalities which disrupts the normal relationships between the stapes, Reichert's cartilage and stapedial muscle. The administration of RA to pregnant mice and the comparison with a genetically induced malformation (the mutation far) provides some interesting information about the postulated mechanisms of human middle ear dysmorphogenesis, as well as precious data about the features of normal ossicular primordia formation. The comparison of these features with human middle ear abnormalities as revealed by medical imaging sheds light on human malformation patterns and provides a better understanding of normal and abnormal radiologic ossicular aspects.

Résumé

L'administration orale d'acide rétinoïque (AR) à des souris gravides à 9 jours de gestation est responsable d'importantes malformations des osselets de l'oreille moyenne, associées à une dysmorphose d'ensemble de la sphère maxillo-faciale évoquant la dysostose mandibulo-faciale humaine. Le malleus, l'incus et le stapes sont affectés. Le malleus présente un manche séparé de sa tête et conservant un rapport constant avec le récessus tubo-tympanique. Le stapes peut ne présenter aucun contact avec la capsule otique. L'atteinte malformative est précocement visible par l'apparition d'un cartilage de Meckel anormalement arciforme au douxième jour, suivie du développement d'ébauches ossiculaires présentant d'emblée une forme anormale. L'administration d'AR à des souris gravides et la comparaison des résultats obtenus avec un modèle génétique (la mutation “far”) est source d'informations très intéressantes relatives aux mécanismes supposés caractériser les dysmorphoses de l'oreille moyenne dans l'espèce humaine. Cette méthodes nous fournit en outre de précieux renseignements relatifs aux caractéristiques de l'ontogenèse ossiculaire normale.

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Authors and Affiliations

  1. Laboratoire d'Anatomie et Embryologie Humaines, Université Libre de Bruxelles, Faculté de Médecine, Route de Lennik 808, B-1070, Bruxelles, Belgique

    S Louryan & R Glineur

  2. Laboratoire d'Anatomie Pathologique et de Microscopie électronqieu, Université Libre de Bruxelles, Faculté de Médecine, Route de Lennik 808, B-1070, Bruxelles, Belgique

    N Dourov

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  1. S Louryan
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  2. R Glineur
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Louryan, S., Glineur, R. & Dourov, N. Induced and genetic mouse middle ear ossicular malformations: a model for human malformative ossicular diseases and a tool for clarifying their normal ontogenesis. Surg Radiol Anat 14, 227–232 (1992). https://doi.org/10.1007/BF01794945

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