Overview

Also Known As:Mecp2^lox

Mice with this X-linked floxed mutation of the methyl CpG binding protein 2 gene may be useful in neurological and developmental studies of Rett syndrome.

Donating Investigator

Adrian Bird, University of Edinburgh

Genetic overview

Genetic Background	Generation
	N7F2 (2020-04-13 00:00:00)

Mecp2^tm1Bird

Allele Type	Gene Symbol	Gene Name
Targeted (Conditional ready (e.g. floxed), No functional change)	Mecp2	methyl CpG binding protein 2

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Research Applications

Neurobiology Research
Research Tools
Mouse/Human Gene Homologs

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Base Price

Starting at:

$255.00 Domestic price for female 4-week

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Details

Detailed Description

These mice possess two functional loxP sites flanking exons 3-4 of the targeted gene on the X chromosome (the donating investigator reports that the middle loxP site is non-functional). Homozygous females and hemizygous males are viable and fertile. Northern blot analysis showed the expected mature transcript from the Mecp2^lox locus as well as a transcript in which the beta-globin intron was unspliced. When these mutant mice are bred to mice that express Cre recombinase, resulting offspring will have exons 3-4 deleted in the cre-expressing tissue(s). Mice with this X-linked floxed mutation may be useful in neurological and developmental studies of Rett syndrome.

For example, when crossed to a strain expressing Cre recombinase in nervous tissue (see Stock No. 003771), this mutant mouse strain develops a neurological phenotype that mimics Rett syndrome.

When crossed to a strain expressing Cre recombinase in GABAergic neurons (see Stock No. 017535), these mice exhibit behaviors common to those seen in Rett Syndrome and Autism Spectrum Disorders.

In an attempt to offer alleles on well-characterized or multiple genetic backgrounds, alleles are frequently moved to a genetic background different from that on which an allele was first characterized. It should be noted that the phenotype could vary from that originally described. We will modify the strain description if necessary as published results become available.

Control Suggestions

000664 C57BL/6J

Additional Information

Considerations for Choosing Controls

Selected References

Guy J; Hendrich B; Holmes M; Martin JE; Bird A. 2001. A mouse Mecp2-null mutation causes neurological symptoms that mimic Rett syndrome. Nat Genet 27(3):322-6PubMed: 11242117 MGI: J:67910

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Genetics

Mecp2^tm1Bird

Allele Symbol: Mecp2^tm1Bird

Allele Name	targeted mutation 1, Adrian Bird
Allele Type	Targeted (Conditional ready (e.g. floxed), No functional change)
Allele Synonym(s)	Mecp2^lox
Gene Symbol and Name	Mecp2, methyl CpG binding protein 2
Gene Synonym(s)
Strain of Origin	129P2/OlaHsd
Chromosome	X
Molecular Note	Insertion of a neomycin resistance cassette into the gene introduced loxP sites that flank exons 3 and 4, and added an intron and polyadenylation signal from the human beta globin gene. From the mutated allele, Northern blot analysis detected the wild type mature transcript and also a transcript in which the beta globin intron was unspliced.
Mutations Made By	Adrian Bird, University of Edinburgh

Disease/Phenotype

Disease Terms

Model with phenotypic similarity to human disease where etiologies involve orthologs. Human genes are associated with this disease. Orthologs of those genes appear in the mouse genotype(s).

Rett syndrome

Research Areas By Phenotype

This mouse can be used to support research in many areas including:

Neurobiology Research
- Neurodevelopmental Defects
  - Rett's syndrome
- Behavioral and Learning Defects
Research Tools
- Cre-lox System
  - loxP-flanked Sequences
- Developmental Biology Research
  - Cre-lox System
Mouse/Human Gene Homologs
- Rett syndrome

Genotype: Mecp2^tm1Bird related

Neurobiology Research
- Ataxia (Movement) Defects

Mammalian Phenotype Terms by Genotype

The following phenotype information is associated with a similar, but not exact match to this JAX^® Mice strain

Genotype: Mecp2^tm1Bird/Y Tg(dlx5a-cre)1Mekk/0
involves: 129P2/OlaHsd * 129S6/SvEvTac * CD-1 * FVB/N

behavior/neurological phenotype

abnormal nest building behavior
- nest building is impaired

decreased startle reflex
- mice show impaired maximum acoustic startle response to 120dB

impaired coordination
- 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

abnormal social investigation
- 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

increased stereotypic behavior
- mice show a 200% increase relative to control in number of holes explored with 2 or more sequential nose pokes in a holeboard assay

nervous system phenotype

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

mammalian phenotype

behavior/neurological phenotype
- Normal - mice show similar grooming times to controls
- Normal - mice exhibit intact olfactory recognition and habituation in response to a novel odorant at 11 weeks of age
- Normal - time exhibiting aggressive behavior such as wrestling, tail-rattling, boxing, and mounting is similar to controls
- Normal - at 12 weeks, mice have intact nociception demonstrated by a hot-plate or tail-flick assay
- Normal - mice have a nonsignificant trend to reduced total distance traveled

mortality/aging
- Normal - mice survive to at least 80 weeks of age

respiratory system phenotype
- Normal - mice show no alterations in tidal volume or minute volume, and display no apneas

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

behavior/neurological phenotype

ataxia
- Normal - however, mice do not exhibit seizures or stereotypical behaviors
- mice develop progressive ataxia that is apparent at 6 weeks and worsens by 20 weeks

impaired coordination
- mice exhibit impaired performance of the marble-burying test, suggesting forelimb incoordination
- mice exhibit reduced latency to fall in both the rotarod and dowel walk assays

abnormal social investigation
- mice spend more time interacting with novel partner mice in a social behavior assay

impaired cued conditioning behavior
- 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
- mice show a diminished acoustic startle response

abnormal gait
- mice develop widely splayed hind limbs after 10 weeks and hind limb retraction after 15 weeks of age

mortality/aging

premature death
- 50% mortality by 29-35 weeks of age

Genotype: Mecp2^tm1Bird/Y Tg(Slc32a1-cre)2.1Hzo/0
involves: 129P2/OlaHsd * 129S6/SvEvTac * FVB/N

growth/size/body region phenotype

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

mammalian phenotype

behavior/neurological phenotype
- Normal - 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
- Normal - animals show no increased interest in a novel object than controls at 11-12 weeks
- Normal - mice display no anxiety-like phenotypes, indicating that hypoactivity or altered social behavior does not result from increased anxiety
- Normal - 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

nervous system phenotype
- Normal - miniature excitatory postsynaptic current quantal size and frequency are similar to controls
- Normal - paired pulse ratio is not significantly altered in neurons

mortality/aging

premature death
- around 50% of mutant mice die by 26 weeks

nervous system phenotype

abnormal miniature inhibitory postsynaptic currents
- 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

abnormal nervous system electrophysiology
- non-seizure hyperexcitability discharges are frequently observed in cultured neurons, but no electrographic seizures are seen

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

reduced long term potentiation
- impaired LTP induced by theta-burst stimulation of Schaffer collaterals is detected

respiratory system phenotype

abnormal respiratory function
- severe respiratory dysfunction is coincident with weight loss

abnormal breathing pattern

respiratory distress

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

apnea
- mice display frequent apneas of greater than 0.4 second durations, coincident with weight loss

behavior/neurological phenotype

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

limb grasping
- after 5 weeks of age, mice show repetitive behavior such as hindlimb clasping

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

increased grooming behavior
- 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
- mice have impaired maximum acoustic startle response than controls to 120 dB at 8 weeks

impaired coordination
- 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

abnormal social investigation
- 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

abnormal spatial learning
- 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

abnormal nest building behavior
- mice are poor nest builders, possibly due to social behavior alterations or to forelimb apraxia at 13 weeks

increased stereotypic behavior
- 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

Genotype: Mecp2^tm1Bird/Y
(129S6.129P2-Mecp2 x FVB/N)F1

behavior/neurological phenotype

abnormal contextual conditioning behavior
- percentage of time spent freezing is elevated relative to wild-type when placed back into the conditioning chamber

decreased anxiety-related response
- mice show decrease anxiety-related behavior in open field assays than wild-type mice

abnormal cued conditioning behavior
- percentage of time spent freezing is elevated relative to wild-type when re-exposure to a previously experienced cue

abnormal social investigation
- 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

abnormal touch/ nociception
- mutants exhibit deficit in pain recognition rather than significant defect in pain sensitivity

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

nervous system phenotype

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

respiratory system phenotype

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

abnormal breathing pattern
- 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

integument phenotype

abnormal touch/ nociception
- mutants exhibit deficit in pain recognition rather than significant defect in pain sensitivity

mammalian phenotype

behavior/neurological phenotype
- Background Sensitivity - no overt abnormalities are observed; mutants do not exhibit impaired coordination in a variety of tests measured
- Normal - mice do not show overt abnormalities like tremor or limb grasping

mortality/aging
- Normal - no early mortality is observed in contrast to Mecp2-null animals

growth/size/body region phenotype
- Background Sensitivity - no size difference is detected relative to wild-type, unlike mice on the C57BL/6 background

Genotype: Mecp2^tm1Bird/Y
(129S6.129P2-Mecp2 x C57BL/6)F1

behavior/neurological phenotype

abnormal nest building behavior
- 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

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

decreased startle reflex
- mice have a decreased startle response relative to wild-type

abnormal social investigation
- 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

abnormal touch/ nociception
- mutants exhibit deficit in pain recognition rather than significant defect in pain sensitivity

increased thermal nociceptive threshold
- mice show increased latency in the hot plate assay

mammalian phenotype

mortality/aging
- Normal - no early mortality is observed in contrast to Mecp2-null animals

nervous system phenotype

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

growth/size/body region phenotype

increased body weight
- 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

integument phenotype

abnormal touch/ nociception
- mutants exhibit deficit in pain recognition rather than significant defect in pain sensitivity

increased thermal nociceptive threshold
- mice show increased latency in the hot plate assay

Genotype: Mecp2^tm1Bird/Y Tg(Nes-cre)1Kln/0
involves: 129P2/OlaHsd * C57BL/6 * SJL

behavior/neurological phenotype

abnormal gait
- develop a stiff, uncoordinated gait

limb grasping

hypoactivity

skeleton phenotype

abnormal tooth morphology
- frequently exhibit uneven wearing of the teeth

craniofacial phenotype

abnormal tooth morphology
- frequently exhibit uneven wearing of the teeth

endocrine/exocrine gland phenotype

cryptorchism

growth/size/body region phenotype

abnormal tooth morphology
- frequently exhibit uneven wearing of the teeth

decreased body weight

mortality/aging

premature death

reproductive system phenotype

cryptorchism

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

behavior/neurological phenotype

increased stereotypic behavior
- mice exhibit repetitive nose-poking behavior in the hole board test
- Normal - 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
- 50% of mice develop spontaneous epileptic seizures starting at 12 weeks

tonic-clonic seizures
- mice show generalized tonic clonic seizures during routine handling

mortality/aging

premature death
- 50% mortality by 29-35 weeks of age

nervous system phenotype

tonic-clonic seizures
- mice show generalized tonic clonic seizures during routine handling

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

Genotype: Mecp2^tm1Bird/Y
involves: 129P2/OlaHsd * C57BL/6J * FVB/N

mammalian phenotype

respiratory system phenotype
- Normal - mice do not exhibit apneas

mortality/aging
- Normal - mice do not show premature lethality

References

Guy J; Hendrich B; Holmes M; Martin JE; Bird A. 2001. A mouse Mecp2-null mutation causes neurological symptoms that mimic Rett syndrome. Nat Genet 27(3):322-6PubMed: 11242117 MGI: J:67910

Additional - Mecp2^tm1Bird related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Standard PCR:Mecp2
- Genotyping resources and troubleshooting
Dietary Information
- LabDiet® 5K52 formulation (6% fat)
Breeding Considerations

Mutant mice were bred to C57BL/6J mice to generate this congenic strain. When maintaining the live congenic colony, females homozygous for this X-linked mutation can be bred with males hemizygous for this X-linked mutation.
- Additional Breeding and Husbandry Support
Mating System
- Homozygote x Hemizygote
Citation
When using the Mecp2^lox mouse strain in a publication, please cite the originating article(s) and include JAX stock #007177 in your Materials and Methods section.

Animal Health Reports

Facility Barrier Level Descriptions

AX10 (Standard)

Pricing & Availability

Available for Pre-order

Domestic
International

Live Mouse

Age

Genotype

Price

weeks

Cryorecovery - Pricing

Service/Product	Description	Price
	X linked - Heterozygous females and males wild-type for Mecp2<tm1Bird>

Related Products and Services

Frozen Mouse Embryo	B6.129P2-Mecp2<tm1Bird>/J	$2595.00
Frozen Mouse Embryo	B6.129P2-Mecp2<tm1Bird>/J	$2595.00
Frozen Mouse Embryo	B6.129P2-Mecp2<tm1Bird>/J	$3373.50
Frozen Mouse Embryo	B6.129P2-Mecp2<tm1Bird>/J	$3373.50

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Also Known As:Mecp2lox

Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Control Suggestions

Additional Information

Selected References

Mecp2tm1Bird

Allele Symbol: Mecp2tm1Bird

Disease Terms

Model with phenotypic similarity to human disease where etiologies involve orthologs. Human genes are associated with this disease. Orthologs of those genes appear in the mouse genotype(s).

Research Areas By Phenotype

This mouse can be used to support research in many areas including:

Genotype: Mecp2tm1Bird related

Mammalian Phenotype Terms by Genotype

Genotype: Mecp2tm1Bird/Y Tg(dlx5a-cre)1Mekk/0involves: 129P2/OlaHsd * 129S6/SvEvTac * CD-1 * FVB/N

behavior/neurological phenotype

nervous system phenotype

mammalian phenotype

Genotype: Mecp2tm1Bird/Y Pvalbtm1.1(cre)Aibs/Pvalb+involves: 129P2/OlaHsd * 129S4/SvJaeSor * 129S6/SvEvTac * C57BL/6J * C57BL/6NCrl

behavior/neurological phenotype

mortality/aging

Genotype: Mecp2tm1Bird/Y Tg(Slc32a1-cre)2.1Hzo/0involves: 129P2/OlaHsd * 129S6/SvEvTac * FVB/N

growth/size/body region phenotype

mammalian phenotype

mortality/aging

nervous system phenotype

respiratory system phenotype

behavior/neurological phenotype

Genotype: Mecp2tm1Bird/Y(129S6.129P2-Mecp2 x FVB/N)F1

behavior/neurological phenotype

nervous system phenotype

respiratory system phenotype

integument phenotype

mammalian phenotype

Genotype: Mecp2tm1Bird/Y(129S6.129P2-Mecp2 x C57BL/6)F1

behavior/neurological phenotype

mammalian phenotype

nervous system phenotype

growth/size/body region phenotype

integument phenotype

Genotype: Mecp2tm1Bird/Y Tg(Nes-cre)1Kln/0involves: 129P2/OlaHsd * C57BL/6 * SJL

behavior/neurological phenotype

skeleton phenotype

craniofacial phenotype

endocrine/exocrine gland phenotype

growth/size/body region phenotype

mortality/aging

reproductive system phenotype

Genotype: Mecp2tm1Bird/Y Ssttm2.1(cre)Zjh/Sst+involves: 129P2/OlaHsd * 129S4/SvJae * 129S6/SvEvTac * C57BL/6

behavior/neurological phenotype

mortality/aging

nervous system phenotype

Genotype: Mecp2tm1Bird/Yinvolves: 129P2/OlaHsd * C57BL/6J * FVB/N

mammalian phenotype

References

Additional - Mecp2tm1Bird related

Genotyping Protocols

Dietary Information

Breeding Considerations

Mating System

Citation

Animal Health Reports

Live Mouse

Cryorecovery - Pricing

Related Products and Services

Payment Terms and Conditions

The Jackson Laboratory's Genotype Promise

Terms Of Use

Licensing Information

JAX® Mice, Products & Services Conditions of Use

No Warranty

Credit for PRODUCTS or SERVICES

Animal Care and Use for SERVICES

No Liability

Also Known As:Mecp2^lox

Mecp2^tm1Bird

Allele Symbol: Mecp2^tm1Bird

Genotype: Mecp2^tm1Bird related

Genotype: Mecp2^tm1Bird/Y Tg(dlx5a-cre)1Mekk/0
involves: 129P2/OlaHsd * 129S6/SvEvTac * CD-1 * FVB/N

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

Genotype: Mecp2^tm1Bird/Y Tg(Slc32a1-cre)2.1Hzo/0
involves: 129P2/OlaHsd * 129S6/SvEvTac * FVB/N

Genotype: Mecp2^tm1Bird/Y
(129S6.129P2-Mecp2 x FVB/N)F1

Genotype: Mecp2^tm1Bird/Y
(129S6.129P2-Mecp2 x C57BL/6)F1

Genotype: Mecp2^tm1Bird/Y Tg(Nes-cre)1Kln/0
involves: 129P2/OlaHsd * C57BL/6 * SJL

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

Genotype: Mecp2^tm1Bird/Y
involves: 129P2/OlaHsd * C57BL/6J * FVB/N

Additional - Mecp2^tm1Bird related