Phenotypes associated with this allele

• Allele Symbol: Myt1l^em1Jdd
• Allele Name: endonuclease-mediated mutation 1, Joseph D Dougherty
• Allele ID: MGI:6741516
• Summary: 2 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Myt1l^em1Jdd/Myt1l^em1Jdd	C57BL/6-Myt1l^em1Jdd/J	MGI:7265076
ht2	Myt1l^em1Jdd/Myt1l^+	C57BL/6-Myt1l^em1Jdd/J	MGI:7265077

Genotype
MGI:7265076

hm1

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

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

mortality/aging

neonatal lethality, complete penetrance ( J:321206 )

• die at birth

Genotype
MGI:7265077

ht2

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

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