The Function of Neurofibromatosis Type 1 Exon 23a Alternative Splicing in Ras/Erk Signaling and Learning Behaviors in Mice

The Function of Neurofibromatosis Type 1 Exon 23a Alternative Splicing in Ras/Erk Signaling and Learning Behaviors in Mice

Bibliographic Details
Main Author: Nguyen, Hieu Thi
Language:English
Published: Case Western Reserve University School of Graduate Studies / OhioLINK 2017
Subjects:
Genetics
Online Access:http://rave.ohiolink.edu/etdc/view?acc_num=case1499440133928005
id ndltd-OhioLink-oai-etd.ohiolink.edu-case1499440133928005
record_format oai_dc
spelling ndltd-OhioLink-oai-etd.ohiolink.edu-case14994401339280052021-08-03T07:03:09Z The Function of Neurofibromatosis Type 1 Exon 23a Alternative Splicing in Ras/Erk Signaling and Learning Behaviors in Mice Nguyen, Hieu Thi Genetics Ras is a key regulator of multiple signaling networks controlling a variety of important biological processes such as cell proliferation, survival, differentiation, and migration. Interestingly, Ras also plays a critical role in the regulation of proper learning and memory. Neurofibromin is one of the most common and well-studied negative regulator of RasGAPs, which inhibits Ras activity. Neurofibromin is the protein product of neurofibromatosis type 1 (NF1) gene, which inactivates the proto-oncoprotein Ras through its GTPase activating protein domain. Mutations on the NF1 gene will cause neurofibromatosis type 1 disease, which is a common human genetic disorder characterized by phenotypes ranging from increased tumor susceptibility to learning disabilities. NF1 alternative exon 23a lies in the center of the GAP domain and is skipped in brain but included in other tissues. To study the molecular and biological functions of this regulated splicing event in vivo, we generated mutant mice (Nf123aIN/23aIN mice) with constitutive Nf1 exon 23a inclusion in all tissues, and found increased Ras activation in their brains. In addition, the brain of Nf123aIN/23aIN mice also has elevated levels of phosphorylated ERK1/2 downstream of Ras. Notably, Nf123aIN/23aIN mice show deficiencies in both short- and long-term spatial learning, as well as in fear associative learning. Taken together, these results strongly suggest that the regulated inclusion of Nf1 exon 23a modulates Ras signaling, and is important for proper learning and memory in mice. Therefore, our knock-in mouse is a very helpful tool for future studies on the role of alternative splicing in Ras/ERK signaling and in learning and memory. 2017-09-07 English text Case Western Reserve University School of Graduate Studies / OhioLINK http://rave.ohiolink.edu/etdc/view?acc_num=case1499440133928005 http://rave.ohiolink.edu/etdc/view?acc_num=case1499440133928005 unrestricted This thesis or dissertation is protected by copyright: some rights reserved. It is licensed for use under a Creative Commons license. Specific terms and permissions are available from this document's record in the OhioLINK ETD Center.
collection NDLTD
language English
sources NDLTD
topic Genetics
spellingShingle Genetics
Nguyen, Hieu Thi
The Function of Neurofibromatosis Type 1 Exon 23a Alternative Splicing in Ras/Erk Signaling and Learning Behaviors in Mice
author Nguyen, Hieu Thi
author_facet Nguyen, Hieu Thi
author_sort Nguyen, Hieu Thi
title The Function of Neurofibromatosis Type 1 Exon 23a Alternative Splicing in Ras/Erk Signaling and Learning Behaviors in Mice
title_short The Function of Neurofibromatosis Type 1 Exon 23a Alternative Splicing in Ras/Erk Signaling and Learning Behaviors in Mice
title_full The Function of Neurofibromatosis Type 1 Exon 23a Alternative Splicing in Ras/Erk Signaling and Learning Behaviors in Mice
title_fullStr The Function of Neurofibromatosis Type 1 Exon 23a Alternative Splicing in Ras/Erk Signaling and Learning Behaviors in Mice
title_full_unstemmed The Function of Neurofibromatosis Type 1 Exon 23a Alternative Splicing in Ras/Erk Signaling and Learning Behaviors in Mice
title_sort function of neurofibromatosis type 1 exon 23a alternative splicing in ras/erk signaling and learning behaviors in mice
publisher Case Western Reserve University School of Graduate Studies / OhioLINK
publishDate 2017
url http://rave.ohiolink.edu/etdc/view?acc_num=case1499440133928005
work_keys_str_mv AT nguyenhieuthi thefunctionofneurofibromatosistype1exon23aalternativesplicinginraserksignalingandlearningbehaviorsinmice
AT nguyenhieuthi functionofneurofibromatosistype1exon23aalternativesplicinginraserksignalingandlearningbehaviorsinmice
_version_ 1719452366691893248

Similar Items