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The Ts65Dn mouse developed at the Jackson Laboratory in Bar Harbor, Maine, has the signature skull and facial deformities of Down's syndrome, strengthening its case as a model for the human syndrome, according to report at the recent AAAS meeting in Washington, DC, Roger Reeves and his associates at Johns Hopkins had previously shown that the mouse has cerebellar deformities in parallel with human Down's syndrome, as well as learning and behavior deficits.

Down's syndrome in humans is marked by three copies of chromosome 21. The mouse model has three copies of its chromosome 16, which is virtually identical to human chromosome 21. In the study presented in Washington (and also published in the January issue of Developmental Dynamics), the researchers found the same pattern of lengthening and shortening of skull and facial bones-leading to skulls flattened at the back and shorter nose--as that found in humans with Down's syndrome.

Down's syndrome is of interest to Alzheimer's researchers because people with the syndrome eventually develop plaques and tangles such as those seen in Alzheimer's. However, this pathology has not been found in the Ts65Dn mouse. "We used three stains and several plaque-specific antibodies, but identified no corresponding pathology in mice up to three years old (that's a VERY old mouse!)," writes Reeve in an email to the Alzheimer Forum.-Hakon Heimer.
References: Richtsmeier JT, Baxter LL, Reeves RH. Parallels of craniofacial maldevelopment in Down's syndrome and Ts65Dn mice. Developmental Dynamics 2000;217:137-145. Abstract

Reeves RH, Irving NG, Moran TH, Wohn A, Kitt C, Sisodia SS, Schmidt C, Bronson RT, Davisson MT. A mouse model for Down's syndrome exhibits learning and behavior deficits. Nat Genet 1995 Oct;11(2):177-84. Abstract

Baxter LL, Moran TH, Richtsmeier JT, Troncoso J, Reeves RH. Discovery and genetic localization of Down's syndrome cerebellar phenotypes using the Ts65Dn mouse. Human Molec Genet 2000 Jan;9:195-202. Abstract

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References

Paper Citations

  1. . Parallels of craniofacial maldevelopment in Down syndrome and Ts65Dn mice. Dev Dyn. 2000 Feb;217(2):137-45. PubMed.
  2. . A mouse model for Down syndrome exhibits learning and behaviour deficits. Nat Genet. 1995 Oct;11(2):177-84. PubMed.
  3. . Discovery and genetic localization of Down syndrome cerebellar phenotypes using the Ts65Dn mouse. Hum Mol Genet. 2000 Jan 22;9(2):195-202. PubMed.

Further Reading

Papers

  1. . Parallels of craniofacial maldevelopment in Down syndrome and Ts65Dn mice. Dev Dyn. 2000 Feb;217(2):137-45. PubMed.
  2. . A mouse model for Down syndrome exhibits learning and behaviour deficits. Nat Genet. 1995 Oct;11(2):177-84. PubMed.
  3. . Discovery and genetic localization of Down syndrome cerebellar phenotypes using the Ts65Dn mouse. Hum Mol Genet. 2000 Jan 22;9(2):195-202. PubMed.

Primary Papers

  1. . Parallels of craniofacial maldevelopment in Down syndrome and Ts65Dn mice. Dev Dyn. 2000 Feb;217(2):137-45. PubMed.
  2. . A mouse model for Down syndrome exhibits learning and behaviour deficits. Nat Genet. 1995 Oct;11(2):177-84. PubMed.
  3. . Discovery and genetic localization of Down syndrome cerebellar phenotypes using the Ts65Dn mouse. Hum Mol Genet. 2000 Jan 22;9(2):195-202. PubMed.