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Published on: May 12, 2015
Altered gene expression in the adult brain of fyn-deficient mice
June Goto1, Tohru Tezuka, Takanobu Nakazawa
1Division of Oncology, Department of Cancer Biology, Institute of Medical Science, University of Tokyo, Tokyo, Japan.
Abstract:
1. Fyn, a member of Src-family tyrosine kinases, is implicated in both brain development and adult brain function. Recent studies have identified some Fyn substrates, however, little is known about the transcriptional targets for Fyn mediated signaling pathways. In the present study, we sought to identify targets downstream of Fyn in vivo. 2. We compared genes expressed in adult hippocampi of wild-type and fyn-deficient mice using gene chips containing more than 12,000 genes. 3. The results showed that 559 transcripts were expressed differentially between these mice. Expression of 20 genes including a substantial number of myelin-associated genes was strongly repressed in fyn-deficient mice. 4. Reduced expression of these myelin-associated genes, such as MBP and MOG, in fyn-deficient mice was also confirmed by real-time PCR and northern blotting, arguing that Fyn is important for function and development of oligodendrocytes. 5. Further analysis of the genes that are differently expressed in fyn-deficient mice may shed light on the molecular mechanism by which Fyn regulates adult neural function.
Insights
Fyn kinase is crucial for brain function, regulating myelin-associated gene expression in adult mice. Its deficiency impairs oligodendrocyte development and function, impacting neural pathways.
Area of Science:
- Neuroscience
- Molecular Biology
- Genetics
Background:
- Fyn, a Src-family tyrosine kinase, plays roles in brain development and function.
- While Fyn substrates are known, its transcriptional targets remain largely uncharacterized.
Purpose of the Study:
- To identify downstream transcriptional targets of Fyn signaling in vivo.
- To elucidate Fyn's role in regulating gene expression within the adult hippocampus.
Main Methods:
- Gene expression profiling using microarrays on adult wild-type and fyn-deficient mouse hippocampi.
- Quantitative analysis of over 12,000 genes.
- Validation of key gene expression changes using real-time PCR and northern blotting.
Main Results:
- 559 differentially expressed transcripts were identified between wild-type and fyn-deficient mice.
- Expression of 20 genes, including myelin-associated genes like MBP and MOG, was significantly repressed in fyn-deficient mice.
- Fyn deficiency impacts oligodendrocyte-related gene expression.
Conclusions:
- Fyn kinase is essential for the expression of myelin-associated genes.
- Fyn plays a critical role in oligodendrocyte function and development.
- Identifying Fyn's transcriptional targets offers insights into its regulation of adult neural function.
