Biology Reference
In-Depth Information
of these data, but data collection methods are more thoroughly dis-
cussed in Chapter 2 . Interested readers can go to the original publica-
tions for more details pertaining to the data sets and the scientific ques-
tions originally addressed through these data. Copies of the original
data are available for download from htt p:// or
http://www . .
1.3.1 Data set 1. Mandibular dysmorphology in a genetically
engineered animal model.
Trisomy 21 or Down Syndrome (DS) is the most frequent live-born ane-
uploidy and results in a characteristic spectrum of developmental per-
turbations affecting many different tissues. Each individual with DS
expresses different subsets of the phenotypes that characterize the
syndrome. Some of these phenotypes (e.g., heart defects) are less com-
mon in DS individuals than other phenotypes. The craniofacial appear-
ance of children with DS occurs in 100% of affected individuals and is
immediately recognizable, although variable (e.g., Kisling, 1966;
Thelander and Pryor, 1966; Frostad, Cleall et al., 1971; Cronk and
Reed, 1981).
Mouse models provide a powerful approach to the identification of
genes whose dosage imbalance contributes to specific aspects of the DS
phenotype. Distal mouse Chromosome 16 (MMU16) demonstrates con-
served linkage with much of human Chromosome 21 (HSA21), the
sequence of which is now known (Hattori et al., 2000). The conserved
linkage spans that portion of the chromosome from the most proximal
known gene called STCH which is located on the q arm of Chr21 to a
gene located in the proximal half of the q arm of Chr21 (21q22.3) called
MX1 (Reeves and Irving et al., 1995; Reeves and Rue et al., 1998;
Baxter and Moran et al., 2000). The Ts65Dn mouse (Davisson,
1990) has been produced and bred so that it is trisomic for most of this
conserved segment of Chr16, meaning that it is at dosage imbalance
for many of the genes indicated in DS (Reeves and Irving et al., 1995).
Ts65Dn mice demonstrate several phenotypic characteristics simi-
lar to those of DS. Reeves et al., (1995) demonstrated impaired per-
formance of Ts65Dn mice in a complex learning task indicating that
dosage imbalance for a gene(s) in this conserved region contributes to
this impairment. Other phenotypes reminiscent of the human DS con-
dition have also been found in the Ts65Dn mouse (Holtzman, 1996;
Baxter, 1998). We were interested in studying these mice to see if they
Search WWH ::

Custom Search