Phenotypes associated with this allele

• Allele Symbol: Mecp2^tm1Bird
• Allele Name: targeted mutation 1, Adrian Bird
• Allele ID: MGI:2137555
• Summary: 8 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cn1	Mecp2^tm1Bird/Y Sst^tm2.1(cre)Zjh/Sst^+	involves: 129P2/OlaHsd * 129S4/SvJae * 129S6/SvEvTac * C57BL/6	MGI:5749568
cn2	Mecp2^tm1Bird/Y Pvalb^tm1.1(cre)Aibs/Pvalb^+	involves: 129P2/OlaHsd * 129S4/SvJaeSor * 129S6/SvEvTac * C57BL/6J * C57BL/6NCrl	MGI:5749563
cn3	Mecp2^tm1Bird/Y Tg(dlx5a-cre)1Mekk/0	involves: 129P2/OlaHsd * 129S6/SvEvTac * CD-1 * FVB/N	MGI:4999644
cn4	Mecp2^tm1Bird/Y Tg(Slc32a1-cre)2.1Hzo/0	involves: 129P2/OlaHsd * 129S6/SvEvTac * FVB/N	MGI:4999647
cn5	Mecp2^tm1Bird/Y Tg(Nes-cre)1Kln/0	involves: 129P2/OlaHsd * C57BL/6 * SJL	MGI:3624719
ot6	Mecp2^tm1Bird/Y	(129S6.129P2-Mecp2^tm1Bird x C57BL/6)F1	MGI:3817461
ot7	Mecp2^tm1Bird/Y	(129S6.129P2-Mecp2^tm1Bird x FVB/N)F1	MGI:3817462
ot8	Mecp2^tm1Bird/Y	involves: 129P2/OlaHsd * C57BL/6J * FVB/N	MGI:4999649

Genotype
MGI:5749568

cn1

• Allelic Composition: Mecp2^tm1Bird/Y; Sst^{tm2.1(cre)Zjh}/Sst⁺
• Genetic Background: involves: 129P2/OlaHsd * 129S4/SvJae * 129S6/SvEvTac * C57BL/6

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

mortality/aging

premature death ( J:228740 )

♂ • 50% mortality by 29-35 weeks of age

behavior/neurological

increased stereotypic behavior ( J:228740 )

♂ • mice exhibit repetitive nose-poking behavior in the hole board test

♂ • however, mice do not exhibit motor deficits or alternations in acoustic startle response, partition, or cued memory tests, or differences in anxiety, pre-pulse inhibition, locomotor activity or long-term potentiation

seizures ( J:228740 )

♂ • 50% of mice develop spontaneous epileptic seizures starting at 12 weeks

tonic-clonic seizures ( J:228740 )

♂ • mice show generalized tonic clonic seizures during routine handling

nervous system

seizures ( J:228740 )

♂ • 50% of mice develop spontaneous epileptic seizures starting at 12 weeks

tonic-clonic seizures ( J:228740 )

♂ • mice show generalized tonic clonic seizures during routine handling

Genotype
MGI:5749563

cn2

• Allelic Composition: Mecp2^tm1Bird/Y; Pvalb^{tm1.1(cre)Aibs}/Pvalb⁺
• Genetic Background: involves: 129P2/OlaHsd * 129S4/SvJaeSor * 129S6/SvEvTac * C57BL/6J * C57BL/6NCrl

mortality/aging

premature death ( J:228740 )

♂ • 50% mortality by 29-35 weeks of age

behavior/neurological

impaired cued conditioning behavior ( J:228740 )

♂ • mice develop progressive cued memory deficits, with the difference in freezing response to a conditioned tone becoming significantly different at 15 weeks of age

decreased startle reflex ( J:228740 )

♂ • mice show a diminished acoustic startle response

ataxia ( J:228740 )

♂ • mice develop progressive ataxia that is apparent at 6 weeks and worsens by 20 weeks

♂ • however, mice do not exhibit seizures or stereotypical behaviors

impaired coordination ( J:228740 )

♂ • mice exhibit reduced latency to fall in both the rotarod and dowel walk assays

♂ • mice exhibit impaired performance of the marble-burying test, suggesting forelimb incoordination

abnormal gait ( J:228740 )

♂ • mice develop widely splayed hind limbs after 10 weeks and hind limb retraction after 15 weeks of age

abnormal social investigation ( J:228740 )

♂ • mice spend more time interacting with novel partner mice in a social behavior assay

Genotype
MGI:4999644

cn3

• Allelic Composition: Mecp2^tm1Bird/Y; Tg(dlx5a-cre)1Mekk/0
• Genetic Background: involves: 129P2/OlaHsd * 129S6/SvEvTac * CD-1 * FVB/N

mortality/aging

mortality/aging ( J:166851 )

♂N • mice survive to at least 80 weeks of age

behavior/neurological

behavior/neurological phenotype ( J:166851 )

♂N • mice show similar grooming times to controls

♂N • mice have a nonsignificant trend to reduced total distance traveled

♂N • time exhibiting aggressive behavior such as wrestling, tail-rattling, boxing, and mounting is similar to controls

♂N • mice exhibit intact olfactory recognition and habituation in response to a novel odorant at 11 weeks of age

♂N • at 12 weeks, mice have intact nociception demonstrated by a hot-plate or tail-flick assay

decreased startle reflex ( J:166851 )

♂ • mice show impaired maximum acoustic startle response to 120dB

impaired coordination ( J:166851 )

♂ • mice display more footslips, shorter latency to fall on wire, reduced number of side touches on dowel and shorter latency to fall from rotarod compared to controls

increased stereotypic behavior ( J:166851 )

♂ • mice show a 200% increase relative to control in number of holes explored with 2 or more sequential nose pokes in a holeboard assay

abnormal nest building behavior ( J:166851 )

♂ • nest building is impaired

abnormal social investigation ( J:166851 )

♂ • mice show increased social interaction with novel and familiar partners; time spent with novel partners is 60% higher than in controls in a 3-chamber assay

nervous system

increased prepulse inhibition ( J:166851 )

♂ • 24 week-old mice show increased prepulse inhibition at 74 dB

respiratory system

respiratory system phenotype ( J:166851 )

♂N • mice show no alterations in tidal volume or minute volume, and display no apneas

Genotype
MGI:4999647

cn4

• Allelic Composition: Mecp2^tm1Bird/Y; Tg(Slc32a1-cre)2.1Hzo/0
• Genetic Background: involves: 129P2/OlaHsd * 129S6/SvEvTac * FVB/N

mortality/aging

premature death ( J:166851 )

♂ • around 50% of mutant mice die by 26 weeks

growth/size/body

weight loss ( J:166851 )

♂ • mice exhibit a period of rapid weight loss preceding death; initial weight gain is normal

behavior/neurological

behavior/neurological phenotype ( J:166851 )

♂N • at 12 weeks of age, mice show similar responses to controls in thermal nociception assays, indicating that the self-injury observed is not due to impaired nociception

♂N • mice display no anxiety-like phenotypes, indicating that hypoactivity or altered social behavior does not result from increased anxiety

♂N • animals show no increased interest in a novel object than controls at 11-12 weeks

♂N • mice recognize and habituate to a novel vanilla odorant; mutants did spend more time sniffing the novel scent than controls (possible manifestation of repetitive behavior) on the first day, but show no differences on the second day

abnormal spatial learning ( J:166851 )

♂ • in a Morris water maze paradigm, animals show a similar rate of learning to control during the 4 training days, but have difficulty locating the platform during the probe trial

increased grooming behavior ( J:166851 )

♂ • time spent grooming is 300% greater than in control mice; excessive grooming leads to fur loss and epidermal lesions in group- and single-housed mice

decreased startle reflex ( J:166851 )

♂ • mice have impaired maximum acoustic startle response than controls to 120 dB at 8 weeks

limb grasping ( J:166851 )

♂ • after 5 weeks of age, mice show repetitive behavior such as hindlimb clasping

impaired coordination ( J:166851 )

♂ • at 5 weeks, mice show increased numbers of footslips on a wire grid and impaired dowel walk at 9 weeks

♂ • mice have a shorter latency to fall on an accelerating rotarod at 19 weeks

decreased grip strength ( J:166851 )

♂ • at 9 weeks, mice show decreased time wire hang time prior to falling and reduce forelimb grip strength compared to controls

decreased locomotor activity ( J:166851 )

♂ • there is a trend to reduced activity observed at 12 weeks, while 19-week old mice are hypoactive

increased stereotypic behavior ( J:166851 )

♂ • male mice begin to show repetitive behaviors after 5 weeks of age such as forelimb stereotypies similar to the mid-line hand-wringing that characterizes Rett syndrome in humans

♂ • animals display a greater tendency to place their nose in the same hole 2 or more sequential times in a holeboard assay for head-dipping stereotypy

abnormal nest building behavior ( J:166851 )

♂ • mice are poor nest builders, possibly due to social behavior alterations or to forelimb apraxia at 13 weeks

abnormal social investigation ( J:166851 )

♂ • mice spend more time showing directed interest (sniffing, pawing, rearing) near the novel partner mouse than displayed by controls in a 3-chamber assay of social interaction at 12-13 weeks

nervous system

nervous system phenotype ( J:166851 )

♂N • miniature excitatory postsynaptic current quantal size and frequency are similar to controls

♂N • paired pulse ratio is not significantly altered in neurons

abnormal nervous system electrophysiology ( J:166851 )

♂ • non-seizure hyperexcitability discharges are frequently observed in cultured neurons, but no electrographic seizures are seen

reduced long-term potentiation ( J:166851 )

♂ • impaired LTP induced by theta-burst stimulation of Schaffer collaterals is detected

abnormal miniature inhibitory postsynaptic currents ( J:166851 )

♂ • amplitude and charge of mIPSCs from layer 2/3 pyramidal neurons of the somatosensory cortex are reduced; no change in frequency is observed

♂ • similar results are observed in autaptic GABAergic striatal neurons

decreased miniature inhibitory postsynaptic current amplitude ( J:166851 )

• in layer 2/3 pyramidal neurons of the somatosensory cortex

increased prepulse inhibition ( J:166851 )

♂ • mice show an increased prepulse inhibition at 78 and 82 dB prepulses at 8 weeks

respiratory system

decreased tidal volume ( J:166851 )

♂ • coinciding with weight loss, mice display a 42% reduction in tidal volume (and 45% reduction in minute volume)

abnormal breathing pattern ( J:166851 )

♂

apnea ( J:166851 )

♂ • mice display frequent apneas of greater than 0.4 second durations, coincident with weight loss

respiratory distress ( J:166851 )

♂

decreased respiration ( J:166851 )

♂ • severe respiratory dysfunction is coincident with weight loss

Genotype
MGI:3624719

cn5

• Allelic Composition: Mecp2^tm1Bird/Y; Tg(Nes-cre)1Kln/0
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6 * SJL

mortality/aging

premature death ( J:67910 )

♂

behavior/neurological

limb grasping ( J:67910 )

♂

abnormal gait ( J:67910 )

♂ • develop a stiff, uncoordinated gait

decreased locomotor activity ( J:67910 )

♂

craniofacial

abnormal tooth morphology ( J:67910 )

♂ • frequently exhibit uneven wearing of the teeth

endocrine/exocrine glands

cryptorchism ( J:67910 )

♂

growth/size/body

abnormal tooth morphology ( J:67910 )

♂ • frequently exhibit uneven wearing of the teeth

decreased body weight ( J:67910 )

♂

reproductive system

cryptorchism ( J:67910 )

♂

skeleton

abnormal tooth morphology ( J:67910 )

♂ • frequently exhibit uneven wearing of the teeth

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Rett syndrome		DOID:1206	OMIM:312750 OMIM:613454	J:67910

Genotype
MGI:3817461

ot6

• Allelic Composition: Mecp2^tm1Bird/Y
• Genetic Background: (129S6.129P2-Mecp2^tm1Bird x C57BL/6)F1

mortality/aging

mortality/aging ( J:135825 )

♂N • no early mortality is observed in contrast to Mecp2-null animals

growth/size/body

increased body weight ( J:135825 )

♂ • Background Sensitivity: a mild increase (animals are about 1 gram heavier) is observed relative to wild-type or F1 mutants from an FVB/N cross

behavior/neurological

decreased startle reflex ( J:135825 )

♂ • mice have a decreased startle response relative to wild-type

impaired coordination ( J:135825 )

♂ • Background Sensitivity: mice display impaired performance in coordination tasks like the rotating rod, hanging wire, and dowel walking tests

abnormal touch/ nociception ( J:135825 )

♂ • mutants exhibit deficit in pain recognition rather than significant defect in pain sensitivity

increased thermal nociceptive threshold ( J:135825 )

♂ • mice show increased latency in the hot plate assay

abnormal nest building behavior ( J:135825 )

♂ • mice show deficits in nest-building relative to wild-type, with fewer animals building or completing nests than wild-type animals over the same time period

abnormal social investigation ( J:135825 )

♂ • mice have altered social behavior and spend more time than wild-type animals interacting with an unfamiliar mouse or with a 'familiar' mouse that has been reintroduced into the cage

nervous system

decreased prepulse inhibition ( J:135825 )

♂ • mice show decreased prepulse inhibition at 74 and 82 decibels compared to wild-type

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Rett syndrome		DOID:1206	OMIM:312750 OMIM:613454	J:135825

Genotype
MGI:3817462

ot7

• Allelic Composition: Mecp2^tm1Bird/Y
• Genetic Background: (129S6.129P2-Mecp2^tm1Bird x FVB/N)F1

mortality/aging

mortality/aging ( J:135825 )

♂N • no early mortality is observed in contrast to Mecp2-null animals

behavior/neurological

behavior/neurological phenotype ( J:135825 )

♂N • Background Sensitivity: no overt abnormalities are observed; mutants do not exhibit impaired coordination in a variety of tests measured

♂N • mice do not show overt abnormalities like tremor or limb grasping

abnormal contextual conditioning behavior ( J:135825 )

♂ • percentage of time spent freezing is elevated relative to wild-type when placed back into the conditioning chamber

abnormal cued conditioning behavior ( J:135825 )

♂ • percentage of time spent freezing is elevated relative to wild-type when re-exposure to a previously experienced cue

decreased anxiety-related response ( J:135825 )

♂ • mice show decrease anxiety-related behavior in open field assays than wild-type mice

increased vertical activity ( J:135825 )

♂ • increased number of vertical explorations is observed compared to wild-type; this is indicative of reduced anxiety

abnormal touch/ nociception ( J:135825 )

♂ • mutants exhibit deficit in pain recognition rather than significant defect in pain sensitivity

abnormal social investigation ( J:135825 )

♂ • mice have altered social behavior and spend more time than wild-type animals interacting with an unfamiliar mouse or with a 'familiar' mouse that has been reintroduced into the cage

nervous system

decreased prepulse inhibition ( J:135825 )

♂ • mice show decreased prepulse inhibition compared to wild-type

respiratory system

abnormal breathing pattern ( J:135825 )

♂ • at 4 months, respiratory pattern is qualitatively different than in wild-type; coefficient of variability of the respiratory rhythm is higher than in wild-type

apnea ( J:135825 )

♂ • increase in apnea incidence (39.5/hour) is observed compared to wild-type (5.8/hour)

growth/size/body

growth/size/body region phenotype ( J:135825 )

♂N • Background Sensitivity: no size difference is detected relative to wild-type, unlike mice on the C57BL/6 background

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Rett syndrome		DOID:1206	OMIM:312750 OMIM:613454	J:135825

Genotype
MGI:4999649

ot8

• Allelic Composition: Mecp2^tm1Bird/Y
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6J * FVB/N

mortality/aging

mortality/aging ( J:166851 )

♂N • mice do not show premature lethality

respiratory system

respiratory system phenotype ( J:166851 )

♂N • mice do not exhibit apneas