description) Dr. Crawford's laboratory has recently identified a number of genes that are induced by oxidative and other stress in hamster HA-1 cells using the method of differential display. When one of these, named adapt78, was cloned and sequenced, it was found to be homologous to a recently reported gene, DSCR1, located in the obligate region of HSA21 where genes associated with Down syndrome, Alzheimer's disease, and other neural disorders are localized. In addition, higher expression of adapt78/DSCR1 mRNA was found in both brain and heart and may be related developmentally to mental retardation and congenital heart disease that are major clinical features of patients with Down syndrome. Thus, adapt78 represents a gene whose overexpression in Down syndrome may produce specific pathogenetic effects due to gene dosage in the trisomic condition. Dr. Crawford proposes specific studies in this RO3 application to determine whether adapt78 plays a role in the etiology of Down syndrome and other stress-related disorders. He proposes to have the NICHD-supported transgenic mouse facility at Alabama generate mice that express human adapt78, following microinjection of a cDNA of human adapt78 under the control of the CMV promoter. Mice identified as positive by PCR will then be studied to determine whether they express adapt78 mRNA, to what level, and in what tissues.
|Narayan, Ananth V; Stadel, Rebecca; Hahn, Amy B et al. (2005) Redox response of the endogenous calcineurin inhibitor Adapt 78. Free Radic Biol Med 39:719-27|
|Kluetzman, Kerri S; Perez, Ana V; Crawford, Dana R (2005) DSCR1 (ADAPT78) lethality: evidence for a protective effect of trisomy 21 genes? Biochem Biophys Res Commun 337:595-601|
|Michtalik, Henry J; Narayan, Ananth V; Bhatt, Nishant et al. (2004) Multiple oxidative stress-response members of the Adapt78 family. Free Radic Biol Med 37:454-62|
|Lin, H Y; Michtalik, Henry J; Zhang, ShenLi et al. (2003) Oxidative and calcium stress regulate DSCR1 (Adapt78/MCIP1) protein. Free Radic Biol Med 35:528-39|
|Suzuki, Toshihide; Spitz, Douglas R; Gandhi, Purvee et al. (2002) Mammalian resistance to oxidative stress: a comparative analysis. Gene Expr 10:179-91|
|Leahy, K P; Crawford, D R (2000) adapt78 protects cells against stress damage and suppresses cell growth. Arch Biochem Biophys 379:221-8|
|Suzuki, T; Higgins, P J; Crawford, D R (2000) Control selection for RNA quantitation. Biotechniques 29:332-7|