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Creating a Chick Embryo Model of Spinal Muscular Atrophy
Author(s) -
Murphy Kelley J.,
Li Ling,
Swoboda Kathryn J.,
Schmid Aloisia
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.626.2
Subject(s) - smn1 , spinal muscular atrophy , electroporation , biology , rna interference , green fluorescent protein , microinjection , microbiology and biotechnology , genetics , gene , rna
Spinal Muscular Atrophy (SMA) is the most common neurodegenerative disease in live births, and is caused by the homozygous deletion of the SMN1 gene and modulated by the amount of protein product of the SMN2 gene. Higher primates are the only animals to carry both the SMN1 and SMN2 genes; all other organisms have the single copy of SMN1 and its deletion causes an embryonic lethal condition. Chick embryos are ideally situated for (1) detection of distinct stages of development, (2) manipulation via electroporation of an interfering RNA (RNAi) construct into the one copy of SMN in the developing chick, and (3) analysis of the resulting deficiency within a short period of time (48 hours) after RNAi introduction. We show that electroporation alone or electroporation of the GFP reporter construct do not cause phenotypic abnormalities which are present with the electroporation of the SMN/GFP RNAi, and that the presence of the SMN/GFP RNAi reduces the amount of SMN protein in the chick as demonstrated by Western Blot and immunohistochemistry. Creating this new model of a common neurodegenerative disease allows us to modulate the severity, and thus more closely mimic the clinical presentation of the disease, by targeting the microinjection/electroporation to earlier or later stages of development; test drug and other interventions; and determine some of the earliest embryonic manifestations of SMA. 1RO1HD054599‐01 to KJS