Genetic modification does not affect the stemness of neural stem cells in nestin promoter-GFP transgenic mice.
Because nestin promoter-GFP mice have frequently been used in neural stem cell (NSC) research, it is essential to prove that there is no alteration in the stemness of NSCs derived from this transgenic model for the interpretation and validity of the data. We compared the stemness of NSCs derived from transgenic mice expressing GFP driven by the nestin enhancer with those from wild-type (C57BL/6) mice with respect to the general gene expression profile, expression of neural stem cell markers as nestin and Sox2, and responsiveness to neurotrophins (BDNF, PDGF-BB, and NT-3). The gene expression profile analysis showed that the coefficient of correlation between the two groups was very high (r=0.9865) in the total genes. We found that 23 genes were either up- or down-regulated more than two-fold in the NSCs from the transgenic mice (p<0.05), without any obvious functional relatedness among them. Likewise, there was no difference between the two mouse groups in the expression of nestin or Sox2, the ability to form neurospheres and the neuronal differentiation of NSCs by neurotrophins. Taken together, the self-renewal and neuronal differentiation ability of NSCs from the transgenic mice showed the great similarity to those from wild-type mice. Such information will be useful when the properties of NSCs are evaluated following genetic modification in such a nestin-GFP Tg model.
Park
Jae Hyun
JH
Department of Pharmacology, National Institute of Toxicological Research, 5 Nokbun-Dong, Eunpyung-Gu, Seoul 122-704, Republic of Korea.
Ahn
Joon Ik
JI
Kim
So Young
SY
Park
Ki Sook
KS
Lee
Young Don
YD
Yamaguchi
Masahiro
M
Chung
Hye Joo
HJ
D000818:Animals; D002452:Cell Count; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D004622:Embryo, Mammalian; D020869:Gene Expression Profiling / Q000379:methods; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics*; D049452:Green Fluorescent Proteins / Q000235:genetics; D007211:Indoles; D007381:Intermediate Filament Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009414:Nerve Growth Factors / Q000494:pharmacology; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D064231:Nestin; D009474:Neurons / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000235:genetics; D055748:SOXB1 Transcription Factors; D013234:Stem Cells / Q000378:metabolism*; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D014404:Tubulin / Q000378:metabolism
D004268:DNA-Binding Proteins; D007211:Indoles; D007381:Intermediate Filament Proteins; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; C577485:Nes protein, mouse; D064231:Nestin; D055748:SOXB1 Transcription Factors; C527783:Sox2 protein, mouse; D015534:Trans-Activators; D014404:Tubulin; C462941:beta3 tubulin, mouse; D049452:Green Fluorescent Proteins; C007293:DAPI