Abstract

Based on the genetic homology between mouse chromosome 16 and human chromosome 21, experimentally induced trisomy 16 mouse has been considered to serve as a suitable model for human Down syndrome. Mice with trisomy 16 express several phenotypic characteristics of human trisomy 21 syndrome; i.e., intrauterine growth retardation, anarsarca, congenital heart disease, brain abnormality, etc. To elucidate morphogenesis of characteristic craniofacial malformation in human Down syndrome, we studied trisomy 16 mouse fetuses that were produced by crossing karyotypically normal C57BL/6 female ice with males carrying the two Robertsonian translocation chromosome Rb(16.17)/Rb(11.16). We examined a series of trisomy 16 conecptuses and their normal littermate controls from day 14 to day 18 of gestation by gross observation and serial microscopic sections. In addition to smaller size and generalized edema, we observed variable, but definite delay in brain and craniofacial development in trisomy 16 mice. The brain revealed less stratified telencephalon, underdeveloped thalamus and hypothalmus with relatively wide third ventricle, and small rhombencephalon. Craniofacial underdevelopment was characterized by persistent open eye, cochlea with fewer turns, delayed closure of the palate, more simple nasal cavity, etc. The tongue was shorter and convex upward, that were especially prominent at 14 days of gestation. The convex tongue and underdeveloped brain made the cranial base convex upward, and the angle between the cranial base an vertebral axis more obtuse. Small head with increase cephalic index and midfacial hypoplasia appeared to account for brain underdevelopment.

• Keywords: Mouse;Trisomy 16;Down syndrome;Malformation;Craniofacial;Brain