Analysis Tools
behavior/neurological
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• mice exhibit increased sensitivity to the 5-HT(2A/2C) receptor agonist 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane-induced head twitch response
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• in the three-chamber test of sociability, mice do not show a preference for another mouse versus an inanimate object
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• mice exhibit an increased startle response at baseline that attenuates with increasing prepulse amplitudes
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• mice spend a greater time hanging from the wire cage lid compared to controls, with mice climbing up to hang briefly on the wire lid and then returning back to the floor of the cage, repeating this behavior on average of 1,000 times over a 24-hour period
• however, no abnormalities in grooming or marble burying are seen
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• in the tube test of social dominance, mice often withdraw from the tube upon encountering an unfamiliar mouse
• however, mice show no differences in anxiety-like behavior on the elevated plus-maze, in the Morris water maze test of spatial learning, in motor memory on the rotarod test, or the forced swim test
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• pups separated from their dam at P7 exhibit a 2-fold decreased in vocalizations compared to control pups
• however, pups exhibit normal body temperature
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cellular
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• the number of proliferating cells per small intestinal crypt is lower
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digestive/alimentary system
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• the number of proliferating cells per small intestinal crypt and per colon crypt are lower
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• small intestinal crypt depth is smaller
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• small intestinal villus height is smaller
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• macromolecular permeability of the mucosa is less than that of wild-type mice
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• the number of proliferating cells per small intestinal crypt is lower
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• propulsive colorectal motility is slower
• treatment with the 5-HT(4) agonist prucalopride via administration to dams from gestation to weaning eliminates the slowing of total GI transit times and of colonic motility
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• colonic migrating motor complexes (i.e. peristaltic reflex) frequency, velocity, and length of propagation are lower, indicating impaired peristaltic reflexes
• prucalopride treatment prevents the decreases in colonic migrating motor complexes frequency, velocity and length of propagation
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• total GI transit time is longer
• however, the rate of gastric emptying and small intestinal transit is normal
• small intestinal transit is slower than in wild-type mice after the injection of exogenous 5-HT
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endocrine/exocrine glands
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• the number of proliferating cells per small intestinal crypt and per colon crypt are lower
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• small intestinal crypt depth is smaller
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homeostasis/metabolism
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• 5-HT levels are increased in whole blood
• however, no change is midbrain or forebrain tissue 5-HT levels is seen
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• mice exhibit increased sensitivity to the 5-HT(1A/7) agonist 8-hydroxy-2-(di-n-propylamino)-tetraline (8-OH-DPAT)-induced hypothermia
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muscle
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• colonic migrating motor complexes (i.e. peristaltic reflex) frequency, velocity, and length of propagation are lower, indicating impaired peristaltic reflexes
• prucalopride treatment prevents the decreases in colonic migrating motor complexes frequency, velocity and length of propagation
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nervous system
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• mice exhibit a hypoplastic enteric nervous system with selective impairment of development/survival of late-born neurons
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• total enteric neurons are less abundant than in wild-type mice, in both the submucosal and the myenteric plexus of the ileum and colon
• sub-mucosal TH-expressing and CGRP-expressing neurons are deficient in absolute terms and as a proportion of total neurons
• mice are deficient in GABA-expressing neurons in the myenteric plexus of the ileum and colon
• density of serotonergic neurons in the intestine is only 36.3% of that found in the intestines of wild-type littermates
• treatment with the 5-HT(4) agonist prucalopride via administration to dams from gestation to weaning prevents the hypoplasia of enteric neurons in both the submucosal and the myenteric plexus, the deficiencies of the submucosal late-born dopaminergic and cGRP-immunoreactive neurons, and of the myenteric late-born GABA+ neurons
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• dorsal raphe 5-HT neurons show a decrease in the firing rate under basal conditions
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• mice exhibit an increase in the rate of hippocampal 5-HT clearance
• mice do not exhibit an increase in 5-HT clearance following infusion of 8-Br-cGMP as seen in wild-type mice
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| autism spectrum disorder | DOID:0060041 | J:202876 , J:237081 | ||
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