A chromosome 21 critical region does not cause specific Down syndrome phenotypes.
The "Down syndrome critical region" (DSCR) is a chromosome 21 segment purported to contain genes responsible for many features of Down syndrome (DS), including craniofacial dysmorphology. We used chromosome engineering to create mice that were trisomic or monosomic for only the mouse chromosome segment orthologous to the DSCR and assessed dysmorphologies of the craniofacial skeleton that show direct parallels with DS in mice with a larger segmental trisomy. The DSCR genes were not sufficient and were largely not necessary to produce the facial phenotype. These results refute specific predictions of the prevailing hypothesis of gene action in DS.
Olson
L E
LE
Department of Physiology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Richtsmeier
J T
JT
Leszl
J
J
Reeves
R H
RH
D000818:Animals; D002872:Chromosome Deletion; D002891:Chromosomes, Human, Pair 21 / Q000235:genetics*; D033481:Chromosomes, Mammalian / Q000235:genetics*; D019465:Craniofacial Abnormalities / Q000235:genetics; D003433:Crosses, Genetic; D004195:Disease Models, Animal; D004314:Down Syndrome / Q000235:genetics* / Q000473:pathology; D005260:Female; D018628:Gene Dosage; D020440:Gene Duplication; D018390:Gene Targeting; D005822:Genetic Vectors; D006801:Humans; D007621:Karyotyping; D008297:Male; D008334:Mandible / Q000002:abnormalities; D051379:Mice; D008810:Mice, Inbred C57BL; D009006:Monosomy; D010641:Phenotype; D011995:Recombination, Genetic; D012886:Skull / Q000002:abnormalities; D014314:Trisomy