American Fancy Rat & Mouse Association

This article is from the Summer 2002 AFRMA Rat & Mouse Tales news-magazine.

Megacecum and Megacolon: Development Disorders in the Enteric Nervous System in Rats

By Carmen Jane Booth, D.V.M.

Prelude: When I originally answered the question regarding distended colon/cecum I was deep in studying and could not devote the time toward writing a detailed answer. I was sent the following comment and asked to respond with more information on the topic. Carmen Jane Booth, D.V.M.

From Debbie “The Rat Lady” Ducommun, Chico, CA
In the fall 2001 issue of Rat & Mouse Tales, someone wrote in asking about weanling rats with “bloat.” Karen Robbins wrote the reply, stating that rats with this condition, megacecum (which is sometimes called megacolon), “usually die within a few days if you don’t euthanize them yourself.”

While I agree with Karen that there is no cure for this genetic disease, there is a treatment. I know of several people who have had very good success treating rats with this condition using the drug cisapride (which helps the large intestines move their contents along), a natural laxative called Senekot, and moist foods. Some of these rats have lived a comfortable, fairly-normal life span with this treatment. For more information, people can refer to my Rat Health Care booklet.

Answer by Carmen Jane Booth, D.V.M.

Normal Anatomy and Physiology

The nervous system consists of three main parts: the brain [central nervous system (CNS)], spinal cord and peripheral nerves [peripheral nervous system (PNS)], and neurons in the gastrointestinal tract [enteric nervous system (ENS)]. Neurons are the functional unit of the nervous system and they are composed of a cell body, dendrites (fibers that receive information), and an axon which transmits the information. The place where neurons transmit information is called a synapse. In essence, this is a gap into which one neuron fiber releases a chemical signal (neurotransmitter) that another neuron recognizes and translates into a message. The nervous system is very complex and literally millions of bits of information are being received, integrated, and responded to all the time.

The ENS begins in the esophagus and extends to the anus. In the human ENS, there are about 100 million neurons, almost as many as in the entire spinal chord. They are responsible for control of gastrointestinal movements and secretion. In the ENS, the neurons are arranged in clusters (plexuses): an outer plexus lying between the longitudinal and circular muscle layers, called the myenteric plexus (Auerbach’s plexus), and an inner plexus called the mucosal plexus (Meissner’s plexus) that lies within the submucosa. The myenteric plexi are responsible for controlling gastrointestinal movements, and the submucosal plexi mainly control gastrointestinal secretion and local blood flow. During development, the neuronal crest cells that will form enteric neurons migrate from the CNS to the gastrointestinal tract (GI) beginning at the esophagus and ending at the anus.

Megacecum vs Megacolon

In rodents, the GI tract is similar to other mammals, except that they have a large cecum which is a blind pouch that extends off the junction of the end of the small intestine and beginning of the large intestine. Massive distension of the cecum is referred to as megacecum and massive distension of the large intestine is referred to as megacolon.

ENS Developmental Disorders

Primary disorders of the ENS can be grouped into those that are characterized by an abnormal number (too many = hyperganglionosis, too few = hypoganglionosis, or none = aganglionosis) of neurons verses neurons whose biochemical or physical properties are abnormal. In either case, the clinical presentation may be similar with varying degrees of bowel obstruction depending upon the extent of the intestinal tract that is affected. In infant and human children, the clinical presentation is frequently dominated by abdominal distension, vomiting, constipation, and pain. As rodents do not vomit, the clinical signs usually consist of progressive abdominal dissension, diarrhea, and eventually death. Congenital intestinal aganglionosis (Hirschsprung disease) is characterized by a complete absence of ganglion cells in the submucosal and myenteric plexi. Diagnosis is by histopathology. The pathogenesis involves failure of neural crest derived neuronal precursors to colonize the entire GI tract during embryogenesis. Mutations in any one of eight different genes affect different stages of the colonization process, despite the similarity of clinical signs. Most of these mutations are either autosomal dominant or autosomal recessive in humans.

In the mouse, there are many different genetic mutations that result in a variable lack of melanin or white spotted coat (Lamoreux, 1999). In the Piebald mouse, the underlying defect is in the endothelin beta receptor (Kapur 1995). In the mid 1980s during my undergraduate years at the University of California, Davis, I had the opportunity to be responsible for maintaining the breeding colony of Piebald mice in the Animal Science Department. At that time the underlying defect was unknown. Mice that were 100% black survived, and mice that were 100% white died. By breeding mice that were no more than 75% white, the colony was able to be continued. Once the genetics were worked out, the breeding plan makes perfect sense. One-hundred percent black mice have two normal copies of the gene (+/+). Mice that are 100% white are embryonic lethal and have two mutant (defective) copies of the gene (-/-). By breeding mice with a high content of white (+/-) the mutation was preserved in the heterozygous state (+/-). The mice (-/-) with the mutation in endothelin receptor beta do not form ganglion cells in the distal large intestine and are nearly devoid of skin melanocytes. This is one of the 8 known genetic mutations that results in the clinical disease known as Hirschsprung disease.

I have been specifically asked to comment on the lines of spotted rats where increased amount of white coincides with increased presence of megacecum/megacolon. Based on what has been published on mice, I would suspect that if it is not a mutation in endothelin receptor beta, than it is probably in one of the other 7 genes known to result in Hirschsprung disease.

In looking up information to answer this question, I was delighted to find that it was Dr. Kapur that wrote the definitive article on the underlying mutation in the Piebald mouse that I had worked with years ago. Three years ago when I started the Ph.D. program at the University of Washington in Seattle, I was fortunate to do a laboratory rotation in Dr. Kapur’s laboratory.

Intestinal dysmotility (abnormal motility) is occasionally associated with increased numbers of ganglion cells (hyperganglionosis) or decreased numbers of ganglion cells (hypoganglionosis) in the enteric plexi. Both are difficult to diagnose. Again there are multiple mutations that have been found, but work in this field continues to find new mutations that cause pseudo-obstruction.

In one paper where this familial megacolon and megacecum arose spontaneously in a colony of Sprague Dawley rats, they found that the disease segregated in a completely penetrant autosomal recessive pattern. Affected rats were normal at birth, but developed marked abdominal distension at 3–14 days and were dead by 41 days of age in all cases. In this specific mutation, there was massive dissension of the proximal colon, cecum, and small intestine, with relative constriction of the mid- and distal large intestine. Histologically, ganglion cells were present throughout the entire GI tract, but on physiology, the frequency and amplitude of spontaneous contractions were reduced in number.


This is a tough question. Anyone who has had intestinal distension from gas can attest to the pain and discomfort, and I would suppose that rodents with megacecum and/or megacolon are also uncomfortable. In terms of breeding good healthy rodents for pets, it would be unethical in my opinion to knowingly breed rats with this condition. It makes no sense to me to breed rats that are going to potentially suffer and die prematurely. I do understand that there are certain coat color patterns that occasionally segregate with megacolon/megacecum in some lines of rats. However, there are other lines with the same coat color patterns that do not contain megacolon/megacecum. In my opinion, it is more humane to euthanize affected rats rather than to try and treat them. It is true that there are a few diligent owners with affected rats that may be successful in keeping the affected rats alive, but at what cost? Is it worth the suffering to all the ones that will not survive? It is an individual choice. In either event, my professional opinion is that affected animals should not be bred. *


  • Cotran, RS, Kumar, V, and Collin, T: Robbins Pathologic Basis of Disease 6th Edition. W.B. Saunders Company 1999. p. 804–805.
  • Guyton, AC and Hall, JE; Textbook of Medical Physiology 9th Edition. W. B. Saunders Company 1996 565–565, 833–834.
  • Kapur, RP: Developmental disorders of the enteric nervous system. Gut 2000 (Suppl IV) ; 47: iv81–iv83.
  • Kapur, RP: Neuropathology of pediatric chronic intestinal pseudo-obstruction and related animal models. Journal of Pathology 2001; 194: 277–288.
  • Kapur RP, Sweetser DA, Doggett B, Siebert JR, Palmiter RD: Intercellular signals downstream of endothelin receptor-B mediate colonization of the large intestine by enteric neuroblasts. Development 1995 Nov;121(11):3787–95
  • Lamoreux, ML: Strain-specific white-spotting patterns in laboratory mice. Pigment Cell Res 1999 Dec;12(6):383–90
  • Lipman, NS et al. Familial megacecum and colon in the rat: a new model of gastrointestinal neuromuscular dysfunction. Laboratory Animal Science 1998; 48: 243–252.

Note: I had the pleasure of doing my first Ph.D laboratory rotation in the Kapur Laboratory at the University of Washington where I had the opportunity to determine and optimize the staining technique for visualization of enteric neurons that contain the neurotransmitter, nitric oxide synthase. Carmen Jane Booth, D.V.M.

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Updated April 10, 2014