Phenotypes Associated with This Genotype

Genotype
MGI:6316332

• Allelic Composition: Slc6a4^tm2.1Rbl/Slc6a4^tm2.1Rbl
• Genetic Background: involves: 129S4/SvJae * 129S6/SvEvTac

• ♀: phenotype observed in females
• ♂: phenotype observed in males
• N: normal phenotype

behavior/neurological

enhanced behavioral response to xenobiotic ( J:202876 )

• mice exhibit increased sensitivity to the 5-HT(2A/2C) receptor agonist 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane-induced head twitch response

abnormal response to social novelty ( J:202876 )

• in the three-chamber test of sociability, mice do not show a preference for another mouse versus an inanimate object

increased startle reflex ( J:202876 )

• mice exhibit an increased startle response at baseline that attenuates with increasing prepulse amplitudes

increased stereotypic behavior ( J:202876 )

• 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

social withdrawal ( J:202876 )

• 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

decreased vocalization ( J:202876 )

• pups separated from their dam at P7 exhibit a 2-fold decreased in vocalizations compared to control pups

• however, pups exhibit normal body temperature

cellular

abnormal small intestinal crypt cell proliferation ( J:237081 )

• the number of proliferating cells per small intestinal crypt is lower

digestive/alimentary system

abnormal crypts of Lieberkuhn morphology ( J:237081 )

• the number of proliferating cells per small intestinal crypt and per colon crypt are lower

abnormal small intestine crypts of Lieberkuhn morphology ( J:237081 )

• small intestinal crypt depth is smaller

decreased small intestinal villus height ( J:237081 )

• small intestinal villus height is smaller

abnormal digestive system physiology ( J:237081 )

• macromolecular permeability of the mucosa is less than that of wild-type mice

abnormal small intestinal crypt cell proliferation ( J:237081 )

• the number of proliferating cells per small intestinal crypt is lower

abnormal gastrointestinal motility ( J:237081 )

• 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

intestinal hypoperistalsis ( J:237081 )

• 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

abnormal intestinal transit time ( J:237081 )

• 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

endocrine/exocrine glands

abnormal crypts of Lieberkuhn morphology ( J:237081 )

• the number of proliferating cells per small intestinal crypt and per colon crypt are lower

abnormal small intestine crypts of Lieberkuhn morphology ( J:237081 )

• small intestinal crypt depth is smaller

homeostasis/metabolism

increased serotonin level ( J:202876 )

• 5-HT levels are increased in whole blood

• however, no change is midbrain or forebrain tissue 5-HT levels is seen

increased physiological sensitivity to xenobiotic ( J:202876 )

• mice exhibit increased sensitivity to the 5-HT(1A/7) agonist 8-hydroxy-2-(di-n-propylamino)-tetraline (8-OH-DPAT)-induced hypothermia

muscle

intestinal hypoperistalsis ( J:237081 )

• 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

nervous system

abnormal enteric nervous system morphology ( J:237081 )

• mice exhibit a hypoplastic enteric nervous system with selective impairment of development/survival of late-born neurons

abnormal enteric neuron morphology ( J:237081 )

• 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

abnormal nervous system electrophysiology ( J:202876 )

• dorsal raphe 5-HT neurons show a decrease in the firing rate under basal conditions

abnormal neurotransmitter uptake ( J:202876 )

• 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

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
autism spectrum disorder		DOID:0060041		J:202876 , J:237081