Phenotypes associated with this allele

• Allele Symbol: Myt1l⁺
• Allele Name: wild type
• Allele ID: MGI:2434962
• Summary: 2 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
ht1	Myt1l^em1Jdd/Myt1l^+	C57BL/6-Myt1l^em1Jdd/J	MGI:7265077
ht2	Myt1l^em1Mwer/Myt1l^+	involves: C57BL/6N	MGI:7328859

Genotype
MGI:7265077

ht1

• Allelic Composition: Myt1l^em1Jdd/Myt1l⁺
• Genetic Background: C57BL/6-Myt1l^em1Jdd/J

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

growth/size/body

obese ( J:321206 )

• difference in weight from controls is observed at P45 and becomes significant at P94

• difference in weight is more pronounced in females than males

limbs/digits/tail

clinodactyly ( J:321206 )

nervous system

abnormal brain development ( J:321206 )

• alterations in chromatin state and gene expression during brain development

• changes in chromatin state are maintained in adult brains

decreased brain size ( J:321206 )

• cortical volume is reduced in proportion with the reduction in brain size

• no change in cell density or ventricular system size

decreased brain weight ( J:321206 )

• at P60

abnormal brain white matter morphology ( J:321206 )

• smaller specific white-matter tracts

decreased corpus callosum size ( J:321206 )

• trend towards reduced volume by Nissl staining that was confirmed by magnetic resonance-based diffusion tensor imaging

abnormal dendritic mushroom spine morphology ( J:321206 )

• decrease in the number of mature mushroom spines and an increase in the number of thin and stubby, immature spines

increased dendritic spine density ( J:321206 )

abnormal dendritic stubby spine morphology ( J:321206 )

• decrease in the number of mature mushroom spines and an increase in the number of thin and stubby, immature spines

abnormal dendritic thin spine morphology ( J:321206 )

• decrease in the number of mature mushroom spines and an increase in the number of thin and stubby, immature spines

abnormal neuron physiology ( J:321206 )

• layer 2/3 pyramidal neurons in the primary visual cortex display significantly depolarized resting membrane potentials and decreased membrane resistance at P21-P23

decreased neuronal precursor proliferation ( J:321206 )

• decreased apical progenitor cell density with normal intermediate progenitor (TBR2+) and postmitotic neuron (TBR1+) density and a decrease in the number of proliferating cells at E14 in the cortex

• increase in the number of recently proliferating cells exiting the cell cycle suggesting precocious differentiation of progenitors

behavior/neurological

behavior/neurological phenotype ( J:321206 )

N • no tremors are seen

impaired cued conditioning behavior ( J:321206 )

• impaired performance in contextual and cued fear conditioning assays suggesting a decrease in associative memory; however, hyperactivity of the mice may confound this result

hyporesponsive to tactile stimuli ( J:321206 )

• reduced sensitivity to stimulation of the plantar surface of the paw with von Frey filaments

decreased grip strength ( J:321206 )

• unable to hold position during the negative geotaxis test

• impaired performance in fore- and hindlimb suspension and grip strength assays

weakness ( J:321206 )

• decreased muscle strength indicated by impaired performance in inverted screen and 90 degree wire assays

• however, performance in balance, coordination, and movement initiation tests is relatively normal

abnormal limb posture ( J:321206 )

• abnormal hindlimb posture with transient hyperflexions of one or both hindlimbs

• hindlimbs are held at the midline but not clasped

hyperactivity ( J:321206 )

• heightened baseline force measurements in the startle task

increased vertical activity ( J:321206 )

♀ • only in females

increased locomotor activity ( J:321206 )

• increase in the distance traveled in an open field assay and in the social operant task

abnormal social/conspecific interaction behavior ( J:321206 )

♂ • males fail to cease nose poking and orient to a social stimulus

decreased aggression towards mice ( J:321206 )

• in a social dominance tube test mice tend to be submissive

decreased social investigation ( J:321206 )

• display decreased sociability in a social approach assay but still exhibiting social preference

excessive vocalization ( J:321206 )

• increased ultrasonic vocalizations by isolated pups suggesting an anxiety like phenotype or increased arousal

• absence of thigmotaxis in the open field assay suggests heightened arousal is more likely than anxiety

cellular

decreased neuronal precursor proliferation ( J:321206 )

• decreased apical progenitor cell density with normal intermediate progenitor (TBR2+) and postmitotic neuron (TBR1+) density and a decrease in the number of proliferating cells at E14 in the cortex

• increase in the number of recently proliferating cells exiting the cell cycle suggesting precocious differentiation of progenitors

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
autosomal dominant intellectual developmental disorder 39		DOID:0070069	OMIM:616521	J:321206

Genotype
MGI:7328859

ht2

• Allelic Composition: Myt1l^em1Mwer/Myt1l⁺
• Genetic Background: involves: C57BL/6N

behavior/neurological

behavior/neurological phenotype ( J:326588 )

N • pups exhibit intact maternal odor preference in the homing test and normal basic motor function

N • social interaction behavior in adulthood appears unaffected, with normal emission of ultrasonic vocalizations during social interactions and during male-female and female-female interactions and normal behavior in the three-chamber assay

N • mice show normal grooming, spatial working memory in the Y-maze, and intact spatial learning and reversal learning

impaired contextual conditioning behavior ( J:326588 )

• mice, especially males, show reduced fear acquisition and contextual fear memory retrieval

abnormal habituation to a new environment ( J:326588 )

• habituation in the activity box is weak

• between-session habituation is weak

decreased anxiety-related response ( J:326588 )

• mice show reduced anxiety-related behavior in the elevated plus maze, spending more time in the open arms than controls

• however, mice do not show differences in locomotor activity in the open field under aversive conditions with bright light and in time spent in the center, or in the number of fecal boli

increased startle reflex ( J:326588 )

♂ • males, but not females, show increased acoustic startle responses to moderate and high sound intensities of 95, 15, and 115 db but no differences at 75 and 85 dB

♂ • males, but not females, show a potentiated startle response during presentation of a pulse of 115 dB in the absence of a pre-pulse

♂ • however, pre-pulse inhibition of acoustic startle is not affected indicating that sensorimotor gating is intact

impaired coordination ( J:326588 )

• overall motor performance on the accelerating rotarod is lower in the standard task and challenge task, particularly on the second day, where the latency to fall is lower during all three trials

• however, motor learning on the accelerated rotarod is intact

increased vertical activity ( J:326588 )

• mice show an increase in rearing in the activity box

increased locomotor activity ( J:326588 )

• mice show higher levels of locomotor activity during the first exposure to the activity box for 30 min, and locomotor activity levels remain high during the second exposure to the activity box the next day

• the increase in locomotor activity is due to a habituation defect

abnormal nest building behavior ( J:326588 )

• nest building behavior is affected, with mice building wider nests; nest width increases faster and to higher levels leading to higher nest quality

excessive vocalization ( J:326588 )

• pups emit more ultrasonic vocalizations of the high-frequency subtype than controls in the homing test

growth/size/body

obese ( J:326588 )

• mice become increasingly overweight

• males gain body weight faster and plateau at a higher level than controls after weaning

• females gain substantially more body weight after weaning and gain so much body weight during late adulthood that they reach body weight levels of males

• however, body weight is normal at P10 and body temperature at P10 and 14 months of age is not affected

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
autosomal dominant intellectual developmental disorder 39		DOID:0070069	OMIM:616521	J:326588