Skip Navigation
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

National Institute of Environmental Health Sciences

Use this QR code to view the newest version of this document
Use this QR code to view the newest version of this document

Your Environment. Your Health.

Publication Detail

Title: Visceral neuropathy and intestinal pseudo-obstruction in a murine model of a nuclear inclusion disease.

Authors: Clarke, Christine M; Plata, Cara; Cole, Bonnie; Tsuchiya, Karen; La Spada, Albert R; Kapur, Raj P

Published In Gastroenterology, (2007 Dec)

Abstract: Intestinal dysmotility is a component of many neurodegenerative disorders, including some characterized by neuronal intranuclear inclusions. PrP-SCA7-92Q transgenic mice phenocopy many aspects of the human polyglutamine neurodegenerative disorder spinocerebellar ataxia type 7 (SCA7). The enteric neuropathology of PrP-SCA7-92Q mice was investigated after observing that they develop signs of intestinal pseudo-obstruction.Gastrointestinal transit of radio-opaque pellets through presymptomatic and symptomatic PrP-SCA7-92Q mice and nontransgenic littermates was compared. Gross, microscopic, and ultrastructural studies were conducted, along with histologic and whole mount immunohistochemistry, to identify intranuclear inclusions and quantify subsets of enteric neurons. Immunoblot analysis was performed to confirm selective loss of particular neuronal populations.A subset of cholinergic enteric ganglion cells in PrP-SCA7-92Q mice harbor nuclear inclusions composed of transgene-derived ataxin-7, which contains a pathogenic polyglutamine expansion. These animals die between 15 and 20 weeks of age with intestinal distension and enterocolitis. Signs of disease are preceded by selective loss of nitric oxide synthase-positive neurons (which lack nuclear inclusions), loss of nerve fibers in the myenteric nerve plexus, and delayed gastrointestinal transit. Cholinergic neurons, including those with inclusions, are spared.PrP-SCA7-92Q mice may be useful models for human intestinal pseudoobstruction, particularly visceral neuropathies with neuronal intranuclear inclusions. Loss of inclusion-free inhibitory neurons supports the hypothesis that inclusions may be neuroprotective or coincidental, as opposed to harbingers of neuron death. Because enteric neuropathology in PrP-SCA7-92Q animals is easily missed by routine histopathology, quantitative immunohistochemical approaches may be required to recognize analogous forms of human enteric neuropathy.

PubMed ID: 18054568 Exiting the NIEHS site

MeSH Terms: No MeSH terms associated with this publication

Back
to Top