Affiliation:
1. Division of Protein and Nucleic Acid Chemistry, MRC Laboratory of Molecular Biology, Cambridge CB2 2QH, United Kingdom
Abstract
ABSTRACT
Hox11
is a homeobox gene essential for spleen formation in mice, since atrophy of the anlage of a developing spleen occurs in early embryonic development in
Hox11
null mice. HOX11 is also expressed in a subset of T-cell acute leukemias after specific chromosomal translocations. Since the protein has a homeodomain and can activate transcription, it probably exerts at least some of its effects in vivo by regulation of target genes. Representational difference analysis has been used to isolate cDNA clones corresponding to mRNA species activated following stable expression of HOX11 in NIH 3T3 cells. The gene encoding the retinoic acid-synthesizing enzyme aldehyde dehydrogenase 1 (Aldh1), initially called Hdg-1, was found to be ectopically activated by HOX11 in this system. Study of
Aldh1
gene expression during spleen development showed that the presence of
Aldh1
mRNA inversely correlated with
Hox11. Hox11
null mouse embryos have elevated
Aldh1
mRNA in spleen primordia prior to atrophy, while
Aldh1
seems to be repressed by
Hox11
during organogenesis of the spleens of wild-type mice. This result suggests that expression of Aldh1 protein is negatively regulated by Hox11 and that abnormal expression of Aldh1 in
Hox11
null mice may cause loss of splenic precursor cells by aberrant retinoic acid metabolism.
Publisher
American Society for Microbiology
Subject
Cell Biology,Molecular Biology
Cited by
42 articles.
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