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Review
. 2015:115:413-58.
doi: 10.1016/bs.ctdb.2015.07.011.

Mouse Models of Rare Craniofacial Disorders

Annita Achilleos  1 , Paul A Trainor  2
Affiliations
Review

Mouse Models of Rare Craniofacial Disorders

Annita Achilleos et al. Curr Top Dev Biol. 2015.

Abstract

A rare disease is defined as a condition that affects less than 1 in 2000 individuals. Currently more than 7000 rare diseases have been documented, and most are thought to be of genetic origin. Rare diseases primarily affect children, and congenital craniofacial syndromes and disorders constitute a significant proportion of rare diseases, with over 700 having been described to date. Modeling craniofacial disorders in animal models has been instrumental in uncovering the etiology and pathogenesis of numerous conditions and in some cases has even led to potential therapeutic avenues for their prevention. In this chapter, we focus primarily on two general classes of rare disorders, ribosomopathies and ciliopathies, and the surprising finding that the disruption of fundamental, global processes can result in tissue-specific craniofacial defects. In addition, we discuss recent advances in understanding the pathogenesis of an extremely rare and specific craniofacial condition known as syngnathia, based on the first mouse models for this condition. Approximately 1% of all babies are born with a minor or major developmental anomaly, and individuals suffering from rare diseases deserve the same quality of treatment and care and attention to their disease as other patients.

Keywords: Cilia; Ciliopathy; Craniofacial; Foxc1; Neural crest cells; Ribosome biogenesis; Ribosomopathy; Syngnathia; Tcof1.

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Figures

Figure 1.
Figure 1.. Contribution of neural crest cells to the craniofacial skeleton.
The cranial neural crest gives rise to the majority of the craniofacial skeleton. All the colored bones in the mouse (left) and human (right) skull are derived from the neural crest.
Figure 2.
Figure 2.. The ribosome biogenesis pathway and ribosomopathies.
Schematic figure summarizing the major stages of ribosome biogenesis. The genes and the corresponding ribosomopathies are depicted. Note that disruption of ribosome biogenesis at different stages leads to different syndromes.
Figure 3.
Figure 3.. Examples of rare craniofacial disorders.
Images of patients with (A) Treacher Collins syndrome, (B) Oral-facial-digital syndrome type 1 [adapted from (Gonzalez, Castro, Nieto, & Bouzan, 2014)], and (C) Syngnathia syngnathia. (D) A 3D CT scan image showing a bilateral fusion of the mandible to the maxilla, an underlying feature of syngnathia.
Figure 4.
Figure 4.. Mouse models of rare craniofacial disorders.
Alizarin red (bone) and alcian blue (cartilage) skeletal staining. (A) Wild-type E18.5 mouse embryo; (B) Tcof1+/− littermate that resembles Treacher Collins syndrome (TCS). (C) Tcof1+/−; p53+/− embryo with normal craniofacial morphology [adapted from (Jones et al., 2008)]. (D) The mandible of a wild-type E18.5 mouse embryo. (E) Mandible of an E18.5 Foxc1−/− embryo fused to the maxilla, which is consistent with syngnathia.
Figure 5.
Figure 5.. The primary cilium and ciliopathies.
Schematic representation of a primary cilium detailing the main compartments of the cilium as well as the products of the genes and their localization and involvement in specific ciliopathies.
See this image and copyright information in PMC

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