2006 Fiscal Year Final Research Report Summary
Production of Down syndrome model mice based on fine genetic information of human chromosome 21.
| Project/Area Number |
16390307
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (B)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Pediatrics
|
|---|
| Research Institution | KEIO UNIVERSITY |
|---|
Principal Investigator |
KUDOH Jun KEIO UNIVERSITY, School of Medicine, Associate Professor (80178003)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
SHIBUYA Kazunori Keio University, School of Medicine, Research Associate (90296723)
SAKAI Kosuke Keio University, School of Medicine, Research Associate (70245463)
TANI Kenji Keio University, School of Medicine, Research Associate (00365420)
|
|---|
| Project Period (FY) |
2004 – 2006
|
| Keywords | Down syndrome / human chromosome 21 / disease model mice / HAC / mouse chromosome 17 / mouse chromosome 10 / BAC / trisomy 21 |
|---|
| Research Abstract |
Down syndrome (DS), or trisomy 21, is caused by the inheritance of three instead of two copies of human chromosome 21 (HC21). It is difficult to identify critical gene(s) for each phenotype because the number of patients with partial trisomy 21 is limited and the phenotype is highly variable in patients with even full trisomy 21. Therefore, mouse models for DS have been generated and used to study phenotype-genotype correlations. We have analyzed transcripts, structure and function of genes on human chromosome 21q22.3. Based on the information, we focus on genes in the regions homologous to mouse chromosomes 10 and 17 to generate novel mouse models for DS. BAC clones containing the entire target gene(s) were selected and transferred into mouse embryonic stem (ES) cells using a human artificial chromosome (HAC) as a vector in collaboration with Dr.Tuneko Okazaki and her colleagues at Fujita Health University. Using these HAC-containing ES cells, we have generated chimeric mice harboring a HAC that carries human chromosome 21 gene(s). Subsequent genetic crossing showed that HAC was stably transmitted to progeny. RT-PCR analysis of three human genes (CBS, U2AF1, CRYAA) on HAC in various tissues of "transminicromosomal (TMC)" mice harboring a HAC revealed that the expression pattern of human genes in mouse tissues is similar to that in human tissues. However, expression level of human CBS gene in various mouse tissues was less than 5% of endogenous mouse counterpart. We speculated that the reduced expression level of human gene was due to species specificities of mouse transcription factors.
|
