Phenotypes associated with this allele

• Allele Symbol: Mecp2^tm1Nlnd
• Allele Name: targeted mutation 1, Nicoletta Landsberger
• Allele ID: MGI:6270401
• Summary: 3 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
ht1	Mecp2^tm1Nlnd/Mecp2^+	involves: 129 * CD-1	MGI:7266283
ot2	Mecp2^tm1Nlnd/Y	involves: 129 * C57BL/6J	MGI:7266261
ot3	Mecp2^tm1Nlnd/Y	involves: 129 * CD-1	MGI:7266266

Genotype
MGI:7266283

ht1

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

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

mortality/aging

mortality/aging ( J:268051 )

♀N • females do not show reduced longevity in the first year of life

growth/size/body

obese ( J:268051 )

♀ • body weight is indistinguishable from wild-type mice at early postnatal days but it progressively increases with aging, leading to obesity

behavior/neurological

abnormal behavior ( J:268051 )

♀ • females start showing Rhett-like features at 9 weeks of age, with worsening of the general condition and mobility, hind limb clasping and tremors

limb grasping ( J:268051 )

♀ • hind limb clasping appears with age

tremors ( J:268051 )

♀ • tremor is the first symptom to appear

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

Genotype
MGI:7266261

ot2

• Allelic Composition: Mecp2^tm1Nlnd/Y
• Genetic Background: involves: 129 * C57BL/6J

mortality/aging

premature death ( J:268051 )

♂ • males die prematurely, with an average lifespan of 97 days

growth/size/body

decreased body weight ( J:268051 )

♂ • males are lighter

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

limb grasping ( J:268051 )

♂ • hind limb clasping appears with age

tremors ( J:268051 )

♂ • tremor is the first symptom to appear

nervous system

decreased brain weight ( J:268051 )

♂ • brains from symptomatic males have a 15.7% weight reduction

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

Genotype
MGI:7266266

ot3

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

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