International Mammalian Genome Society


The 13th International Mouse Genome Conference
October 31-November 3, 1999

Table of Contents * Structure * Bioinformatics * Sequence * Mapping * New Tools * Gene Discovery * Developmental * Mutagenesis * Functional Genomics

F10 Ts65Dn - A Mouse Model for Down Syndrome

Muriel T. Davisson, Lawrence J. Bechtel, Cecilia Schmidt, Roderick T. Bronson, and Alberto C. S. Costa. The Jackson Laboratory, Bar Harbor, Maine

Ts(1716)65Dn is the first mouse model for Down syndrome that survives to adulthood. These mice are segmentally trisomic for most of the segment conserved between human Chr 21 and mouse Chr 16. At least 27 conserved genes have been identified that are in the ~10-12 Mb segment. Initial characterization of Ts65Dn mice has focused on behavioral and learning deficits. They have impaired learning and memory in the Morris water maze and behavioral anomalies, including locomotor hyperactivity, lack of behavioral inhibition, and stereotypic behavior.1-7 Although the brains appear normal by visual inspection and in standard H&E-stained histologic preparations, they show age-related degeneration of basal forebrain cholinergic neurons, astrocytic hypertrophy, and increased astrocyte numbers.3 Trisomic females have smaller and fewer litters than euploid females; trisomic males are effectively sterile with hypospermia. To characterize general pathology in the Ts65Dn mice we carried out a longitudinal study following over 50 Ts65Dn mice and 50 euploid littermate controls from birth to death and assessed pathologic lesions at death. When mice appeared moribund, they were deeply anesthetized and perfused with Bouin's fixative. Most Ts65Dn mice showed a growth curve similar to controls but delayed, declined in weight earlier in life, and had a reduced life span. T-cell populations by FACS analysis were not abnormal but red blood cell analysis suggested a mild macrocytic anemia. The pattern of pathologic lesions observed in Ts65Dn mice was generally no different from the pattern found in normal littermate controls and other studies of aging mice, except for increased incidences of mild to severe hydrocephalus, aspermia and testicular atrophy. We have also recently shown that several motor coordination and functions are impaired in Ts65Dn mice. Our findings indicate that Ts65Dn mice share many (but not all) of the features associated with DS, and adds evidence for the value of Ts65Dn as a model system for the mental deficit aspects of DS. We also will report preliminary data using the model to assess expression of mouse Chr 16 genes that may be involved in features of the DS phenotype.

1Coussons-Read and Crnic, Behav Genet 1996, 26:7-13.
2Escorihuela et al., Neurosci Lett 1995, 199:143-6.
3Holtzman et al., Proc Natl Acad Sci USA 1996, 93:13333-38.
4Reeves et al., Nat Genet 1995, 11:177-83.
5Klein et al., Physiol Behav 1996, 60:1159-64.
6Demas et al., Behav Brain Res 1998, 90:199-201.
7Dierssen et al., Brain Res1997, 749:238-44.

 


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