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[P38]: Retinoic acid downregulates microRNAs to induce myelomeningocele in rat
Author(s) -
Jun Z.J.,
Guang S.D.,
Ju W.,
Yong Z.C.,
Xu M.
Publication year - 2006
Publication title -
international journal of developmental neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.761
H-Index - 88
eISSN - 1873-474X
pISSN - 0736-5748
DOI - 10.1016/j.ijdevneu.2006.09.101
Subject(s) - medicine , library science , retinoic acid , political science , chemistry , computer science , biochemistry , gene
Huntington’s disease is a devastating hereditary neurological disorder caused by the expansion of a polyglutamine repeat stretch in the amino terminus of the huntingtin protein. It is currently unknown how the mutation gives rise to the disease, however there is increasing evidence to suggest that some of the pathology may be attributable to a perturbation of huntingtin’s normal function. Currently the precise function of huntingtin is unknown, therefore an analysis of its normal role may provide some understanding of the cause of the pathology associated with Huntington’s disease. Previous studies have shown that homozygous knock-out of huntingtin in mice is embryonic lethal (E7.5) demonstrating an essential role in early embryonic development (Duyao et al., 1995). Heterozygous huntingtin knock-out mice however show no phenotype. In this study, zebrafish has been used as a model system to analyse the role of huntingtin in development. Antisense morpholino oligonucleotides were used to reduce huntingtin protein expression to a level so as to by-pass this early lethality however still provide a clear phenotypic profile. Importantly, using this model system, we are able to gain easy access to early stage embryos for a more detailed analysis of the effects of huntingtin deficiency. Using this model, we have identified a number of interesting phenotypes that may shed light on the role of huntingtin during development. We have demonstrated a disruption in the formation of various specific brain structures associated with the peripheral nervous system and neural crest. The disruption in these regions suggest that huntingtin may play an important role in the formation of these structures and further analysis of these phenotypes have allowed us to pin point the stage at which this disruption is occurring. These studies have provided support to the theory that huntingtin plays a role during development and have revealed a specific role for huntingtin in early neuronal cell populations.