Phenotypes Associated with This Genotype

Genotype
MGI:6394127

• Allelic Composition: Shank3^tm2.1Bux/Shank3^tm2.1Bux
• Genetic Background: B6(Cg)-Shank3^tm2.1Bux

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

nervous system

decreased prepulse inhibition ( J:270363 )

• changes in pre-pulse inhibition of acoustic startle are consistent with abnormalities in auditory processing, rather than sensorimotor gating deficits

mortality/aging

premature death ( J:270363 )

• mice show higher numbers of death between 18 and 22 months

neonatal lethality, incomplete penetrance ( J:270363 )

• 6.9% of pups die between birth and P1

behavior/neurological

impaired contextual conditioning behavior ( J:270363 )

• mice show an impairment in contextual learning, showing a decrease of freezing during the habituation of the training session

enhanced cued conditioning behavior ( J:270363 )

• mice show an enhancement of freezing postcues during cued testing

abnormal habituation to a novel odor ( J:270363 )

• adults show little response to nonsocial scents (water, banana, and lemon)

• however, mice show normal response to social scents indicating that mice do not have anosmia

• adults show deficits in the buried food test, with only 7 of 19 mice able to retrieve food in less than 2 minutes and 9 of 19 mice not able to find the food at all

impaired spatial learning ( J:270363 )

• mice show a one day delay in the initial learning to find the escape hatch and a delay in learning the new position of the escape hatch in the Barnes maze

• in the probe test of the Barnes maze, mice spend equal time in both the new and old targets, indicating impaired reversal learning

• however, no differences are seen in the Y-maze spontaneous alternation test indicating working memory is not altered

increased anxiety-related response ( J:270363 )

• in the elevated zero-maze, mice spend less time in the open arcs than controls but do not show a difference in preference for the closed arcs versus open arcs

• mice show a decrease of the duration of head dipping exploratory behavior in the open arcs of the elevated zero-maze

• long-lasting spontaneous freezing during the habituation and before the sound-shock association in fear conditioning training indicate increased anxiety

• however, no differences in the open field thigmotaxis are seen

increased fear-related response ( J:270363 )

• in the fear conditioning test, mice show higher levels of freezing compared to controls during the training session in post-shock freezing

abnormal response to novel object ( J:270363 )

• mice show a decrease in time spent exploring objects in the 4-object exploration test

• mice show a strong avoidance toward inanimate objects and spend excessive time in the corners of the open field rather than investigating a novel or familiar object

• in the marble burying test, mice leave the marbles almost completely undisturbed for the whole duration of the test

• mice show increased escape attempts in the four-object interaction test and in the marble burying test but not during the buried food test, indicating that escape behavior is elicited by the presence of unfamiliar objects in the testing cage

• object avoidance may explain the reduction of the total time of direct interactions with the applicator used to present different scents during olfactory habituation and dishabituation test

increased grooming behavior ( J:270363 )

• mice engage in longer episodes of self-grooming

• however, the number of spontaneous grooming bouts is normal

abnormal impulsive behavior control ( J:270363 )

• the latency to start turning in the negative geotaxis test and the stort crossing in the beam walking test are lower demonstrating impulsive behavior

abnormal reflex ( J:270363 )

• in the wire suspension and grasping reflex, acquisition of the response is delayed and mice remain impaired until time of weaning

• however, adults show no abnormalities in pinna reflex, palpebra reflex, toe pinch retraction test, Preyer reflexes, or visual placing/reaching reflexes

premature suckling reflex loss ( J:270363 )

• pups show a premature disappearance of the rooting reflex

• however, acquisition of the rooting reflex is normal

• however, other sensory-motor and neurologic milestones such as cliff aversion, ear twitch, surface righting, and open field crossing are not affected and eye opening, ear opening, tooth eruption, and fur development are normal

abnormal righting response ( J:270363 )

• mice show a delay in the response to the mid-air righting task, although all mice are able to respond properly at the end of the observation period

decreased startle reflex ( J:270363 )

• mice show a delay in the response to auditory startle, although all mice are able to respond properly at the end of the observation period

• adults show a reduced startle response throughout all sound intensities (74-92 dB) indicating impaired sound discrimination

impaired coordination ( J:270363 )

• adults show shorter latencies to fall in the accelerating rotarod test and fail to improve over time

• mice show impairment of motor coordination and balance in the beam walking test

weakness ( J:270363 )

• adults show reduced strength and endurance in the inverted screen and hanging tests

• however, no differences in forelimb grip strength are seen

abnormal locomotor activation ( J:270363 )

• in the negative geotaxis test, an initial delay is seen at P5, with mice falling or staying in the starting position, however, most mice master the task by P9

• after P9, mice show higher reactivity in the negative geotaxis test characterized by a shorter latency to turn

• adults show a shorter latency to turn in the negative geotaxis test

long stride length ( J:270363 )

• mice show an increase in stride length

• however, stance and sway are normal

decreased vertical activity ( J:270363 )

• mice show a decrease in the total number of rear times in the open field

decreased locomotor activity ( J:270363 )

• adults show reduced spontaneous locomotion in the open field

• however, adult mice show no abnormalities in spontaneous general activity, stereotypies, transfer arousal, gait, pelvic and tail elevation

hyperactivity ( J:270363 )

• hyperactivity is seen during handling

• adults show a higher score in the touch escape test, a lower score in positional passivity, and a shorter latency to move from the beam during the catalepsy test, indicating hyperactivity

circling ( J:270363 )

• mice exhibit more rotations

abnormal nest building behavior ( J:270363 )

♀ • nest built by mutants are less elaborate than those built by wild-type mice, with some mice leaving the nesting material completely untouched

abnormal sexual interaction ( J:270363 )

♂ • males show an increase in latency for the first event of anogenital sniffing, however sniffing duration during male-female social interaction and sniffing latency to body and nose are normal

♂ • however, mice show normal sociability in the three-chambered test

decreased vocalization ( J:270363 )

• mice spend less time calling and have shorter calls

• P6 mice emit fewer ultrasonic vocalizations

growth/size/body

postnatal growth retardation ( J:270363 )

• growth rate of pups is slower and by P14, mice weigh less than wild-type mice

• neonates show a developmental delay

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Phelan-McDermid syndrome		DOID:0080354	OMIM:606232	J:270363