International Mammalian Genome Society

logo18th International Mouse Genome Conference

17-22 October 2004, Seattle, USA


POSTER 161 - NEURAL CREST DEFICIT IN CRANIOFACIAL SKELETON PRECURSORS OF TS65DN MICE, A MODEL FOR DOWN SYNDROME

Roper RJ, Reeves RH

Johns Hopkins University School of Medicine, Baltimore, United States

Ts65Dn mice display several phenotypic similarities to Down syndrome (DS) including craniofacial dysmorphology, a distinguishing feature found in all DS individuals.  Neural crest cells (NCC) contribute prominently to the craniofacial skeleton affected in DS and the Ts65Dn mouse.  Because many tissues affected in DS have a NCC component, it has been hypothesized that trisomy 21 causes a defect in NCC.  However, no direct experiments have proven or disproven an effect on NCC in DS.  To examine the hypothesis that trisomy affects NCC and therefore contributes to the etiology of DS craniofacial dysmorphology, we bred Ts65Dn mice with mice homozygous for the Wnt1-lacZ transgene which is expressed predominantly in NCC at embryonic day 9.5 (E9.5). Ts65Dn x Wnt1-lacZ offspring were dissected at E9.5 and exhibited lacZ-marked cranial NCC.  Trisomic and euploid embryos were identified by FISH analysis of the yolk sac and age-matched by somite number.  Although the frequency of Ts65Dn at weaning is 25-30%, we observed no deviation from Mendelian ratios at E9.5.  Additionally, the average somite number in E9.5 trisomic and euploid mice was not significantly different and provided no evidence for “developmental delay” of Ts65Dn mice.  Unbiased stereological techniques revealed both NCC number and volume of the 1st pharyngeal arch were reduced in Ts65Dn vs. euploid littermates, demonstrating an effect of trisomy on NCC and craniofacial skeleton precursors.  Further analysis of embryos at additional somite-specific developmental stages will investigate the molecular etiology of the NCC deficit and its contribution to craniofacial skeletal dysmorphology in Ts65Dn mice.

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