Phenotypes Associated with This Genotype

Genotype
MGI:7266266

• Allelic Composition: Mecp2^tm1Nlnd/Y
• Genetic Background: involves: 129 * CD-1

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

mortality/aging

premature death ( J:268051 )

♂ • males die prematurely, with an average lifespan of 121 days

growth/size/body

slow postnatal weight gain ( J:268051 )

♂ • males show a tendency to be lighter soon after birth

increased body weight ( J:268051 )

♂ • while males show a tendency to be lighter soon after birth, they become generally overweight in adulthood

behavior/neurological

abnormal behavior ( J:268051 )

♂ • males become progressively symptomatic with Rett-like features after weaning, with worsening of the general condition, tremors, hind limb clasping and highly variable altered mobility

♂ • however, no differences are seen in anxiety and exploration in the light and dark test, emergence test, or novelty test

impaired cued conditioning behavior ( J:268051 )

♂ • males show impaired tone (conditioned stimulus) memory at P30 and P60 during the auditory fear conditioning test, showing reduced freezing during the cue exposure 24 hours after training

abnormal spatial working memory ( J:268051 )

♂ • in the spontaneous alternation test, P30 males show more than a 30% reduction of correct alternation with the same number of entries indicating impaired working memory

limb grasping ( J:268051 )

♂ • hind limb clasping appears with age

tremors ( J:268051 )

♂ • tremor is the first symptom to appear

impaired coordination ( J:268051 )

♂ • P30 males show altered motor coordination on the rotarod and increased muscle fatigue

decreased grip strength ( J:268051 )

♂ • grip strength is decreased at P30 and P60

short stride length ( J:268051 )

♂ • gait analysis shows decreased stride length at P30 which is further decreased at P60

decreased locomotor activity ( J:268051 )

♂ • decrease in spontaneous locomotor activity

muscle

increased muscle fatigability ( J:268051 )

♂ • P30 males show increased muscle fatigue on the rotarod

nervous system

decreased brain weight ( J:268051 )

♂ • brains show an overall weight reduction of 12%, 13.5%, and 17.5% at P18, P40, and P>130, respectively

abnormal neuron physiology ( J:268051 )

♂ • cultured E15.5 cortical neurons show a reduced amplitude of KCl-induced calcium transients at DIV4 and DIV13, indicating an impairment in the sensitivity of voltage-operated calcium channels and defective neuronal responsiveness to depolarization

♂ • immature neurons show a reduction in NMDA-induced calcium peaks, however mature neurons exhibit normal calcium transients associated with NMDA stimulation despite lower response to KCl

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Rett syndrome		DOID:1206	OMIM:312750 OMIM:613454	J:268051