Navigation Links
Study links APC gene to learning and autistic-like disabilities
Date:6/17/2014

BOSTON (June 17, 2014, 4:00 a.m. EDT) Autistic-like behaviors and decreased cognitive ability may be associated with disruption of the function of the Adenomatous Polyposis Coli (APC) gene. When Tufts researchers deleted the gene from select neurons in the developing mouse brain, the mice showed reduced social behavior, increased repetitive behavior, and impaired learning and memory formation, similar to behaviors seen in individuals with autism and intellectual disabilities. This study is the first to evaluate how the loss of APC from nerve cells in the forebrain affects brain development, learning, and behavior. The research team, led by Michele Jacob, Ph.D., engineered a new mouse model for studying cognitive and autistic-like disabilities. The study was published online today in Molecular Psychiatry.

In addition to observing autistic-like behaviors and cognitive impairments in the mice, researchers found significant molecular changes in the brain. Eliminating APC chiefly from the excitatory neurons in the forebrain led to altered levels of specific proteins that regulate gene expression and influenced the structure, number, and function of synapses.

Some of these molecular changes have not been seen in other genetic mouse models of cognitive and autistic-like disabilities, but are likely relevant to the human disorders based on recently identified risk genes. The researchers propose that APC tightly regulates particular protein levels, maintaining them within a range that is critical to normal learning and memory consolidation.

"What makes this study interesting is that although there are hundreds of risk genes implicated in autism, the removal of this single gene produced a multi-syndromic disorder similar to that seen in individuals with both cognitive deficits and autism. The APC-deficient mice are noticeably different from normal mice in their impaired learning, poor memory consolidation, repetitive behaviors, and reduced social interest," said co-first author Jonathan Alexander, a Ph.D. candidate in neuroscience at the Sackler School of Graduate Biomedical Sciences at Tufts and a member of the Michele Jacob lab at Tufts University School of Medicine.

"This APC knock-out mouse is different because APC is eliminated from a specific type of cell in the brain during a critical period of development. This leads to deregulation of key signaling pathways and produces the cognitive and behavioral changes that we observed," explained co-first author Jesse Mohn, Ph.D., a graduate of the Sackler School and now a scientist at Galenea Corp.

"APC loss leads to molecular changes predicted to resemble, at least in part, those caused by spontaneous mutations in another gene, CHD8, recently identified as a high confidence risk factor for sporadic autism, that is, autism that arises spontaneously rather than inherited genetic mutations from parents. Thus, our findings are relevant to autism and intellectual disabilities caused by other human gene mutations, not only APC," said senior author Michele Jacob, Ph.D., professor of neuroscience at Tufts University School of Medicine, and member of the Cell, Molecular and Developmental Biology; Cellular and Molecular Physiology; and Neuroscience program faculties at the Sackler School.

"This study demonstrates the vital role that APC plays as a central hub that links to and regulates multiple signaling pathways within nerve cells that are essential for normal cognition and social behavior," added Antonella Pirone, Ph.D., a co-author and postdoctoral scholar in the Jacob lab. "We hope that identifying these novel molecular and functional changes caused by APC loss will contribute to the development of effective treatments for autism and cognitive impairments in patients."

Tufts University has filed patent applications claiming the use of the new mouse model for the screening of improved therapeutics.


'/>"/>

Contact: Siobhan E. Gallagher
siobhan.gallagher@tufts.edu
617-636-6586
Tufts University, Health Sciences Campus
Source:Eurekalert

Related biology news :

1. Study by UC Santa Barbara researchers suggests that bacteria communicate by touch
2. Law that regulates shark fishery is too liberal: UBC study
3. New study will help protect vulnerable birds from impacts of climate change
4. Study jointly led by UCSB researcher supports theory of extraterrestrial impact
5. BYU study: Using a gun in bear encounters doesnt make you safer
6. 15-year study: When it comes to creating wetlands, Mother Nature is in charge
7. Pycnogenol (French maritime pine bark extract) shown to improve menopause symptoms in new study
8. Crystal structure of archael chromatin clarified in new study
9. EU-funded study underlines importance of Congo Basin for global climate and biodiversity
10. University of Houston study shows BP oil spill hurt marshes, but recovery possible
11. Study demonstrates cells can acquire new functions through transcriptional regulatory network
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:2/9/2016)... (NASDAQ: AWRE ), a leading supplier of biometrics software and ... ended December 31, 2015.  --> ... million, an increase of 61% compared to $4.3 million in the ... 2015 was $2.6 million compared to $0.2 million in the fourth ... Higher revenue and operating income in the fourth quarter of ...
(Date:2/4/2016)... 2016 The field of Human Microbiome ... most popular hubs of the biotechnology industry. While ... studies of human microbiota, have garnered a lot ... microbiome space has literally exploded in terms of ... report focuses on biomedical aspects of research, development, ...
(Date:2/3/2016)... 2016 http://www.researchandmarkets.com/research/d8zjcd/emotion_detection ... "Emotion Detection and Recognition Market by ... Software Tools (Facial Expression, Voice Recognition and ... - Global forecast to 2020" report ... http://www.researchandmarkets.com/research/d8zjcd/emotion_detection ) has announced the addition of ...
Breaking Biology News(10 mins):
(Date:2/11/2016)... 2016 --> ... (OTCQB: PSID), a life sciences company focused on ... subsidiary, which markets the Caregiver® FDA-cleared non-contact thermometer, ... January 2016, including entering into agreements with five ... growth, and establishing several near-term pipeline opportunities. ...
(Date:2/11/2016)... ... 11, 2016 , ... Reichert Technologies, which has created advanced ... the highest level of accuracy and quality with the addition of two new ... Refractometer. Accurate, reliable and tough enough for the most demanding applications, these ...
(Date:2/11/2016)... ... February 11, 2016 , ... Global Stem Cells ... in Quito, Ecuador. The new facility will provide advanced protocols and state-of-the-art techniques ... the world. , The new GSCG clinic is headed by four prominent ...
(Date:2/10/2016)... 2016 Early-career researchers from ... , Uganda and Yemen ... and nutrition   Indonesia , Nepal ... and Yemen are being honored for their accomplishments ... also celebrated for mentoring young women scientists who are pursuing careers in ...
Breaking Biology Technology: