Mecp2<tm1Hzo> Targeted Allele Detail MGI Mouse (MGI:2183727)

Mecp2^tm1Hzo
Targeted Allele Detail

Nomenclature

Symbol:	Mecp2^tm1Hzo
Name:	methyl CpG binding protein 2; targeted mutation 1, Huda Zoghbi
MGI ID:	MGI:2183727
Synonyms:	Mecp2³⁰⁸
Gene:	Mecp2 Location: ChrX:71271931-71331029 bp, - strand Genetic Position: ChrX, 29.6 cM

Mutation
origin

Germline Transmission:	Earliest citation of germline transmission: J:78009
Parent Cell Line:	AB2.2 (ES Cell)
Strain of Origin:	129S7/SvEvBrd-Hprt1^b-m2

Mutation
description

Allele Type:	Targeted (knock-out)
Mutation:	Disruption caused by insertion of vector
	A stop codon and a floxed neo cassette were inserted into exon 4. The stop codon was inserted downstream of codon 308, allowing translation of the methyl-CpG binding domain and the transcriptional repression domain. Western blot analysis showed that only truncated protein was present in homozygous mutant mice. Staining of brain tissue with a carboxy terminal antibody confirmed the absence of normal protein. (J:78009)

Find Mice (IMSR)

Mouse strains and cell lines available from the International Mouse Strain Resource (IMSR)

Carrying this Mutation:	Mouse Strains: 1 strain available Cell Lines: 0 lines available
Carrying any Mecp2 Mutation:	12 strains or lines available

Phenotype
summary

Phenotype Summary by Mammalian Phenotype terms

(show or hide all annotated terms)

Genotypes are listed in the next section.

Key:

hm	homozygous	ht	heterozygous
cn	conditional genotype	cx	complex: > 1 genome feature
tg	involves transgenes	ot	other: hemizygous, indeterminate,...
N	normal phenotype		expected model not found

Affected Systems	Genotypes:	ht1	ot2	ot3
behavior/neurological		√	√	√
abnormal behavior		√
increased anxiety-related response				√
abnormal motor capabilities/coordination/movement				√
abnormal involuntary movement		√	√	√
tremors		√	√	√
impaired coordination		√	√	√
abnormal locomotor activity				√
decreased vertical activity				√
hypoactivity				√
abnormal social investigation				√
seizures				√
		ht1	ot2	ot3
cellular				√
abnormal nucleus morphology				√
		ht1	ot2	ot3
life span/aging				√
premature death				√
		ht1	ot2	ot3
nervous system				√
seizures				√
		ht1	ot2	ot3
skeleton				√
kyphosis				√
		ht1	ot2	ot3
skin/coat/nails				√
disheveled coat				√
greasy coat				√

		ht1	ot2	ot3
Disease Models		√	√	√
Rett Syndrome; RTT		√	√	√

Phenotypic
data by
genotype

Phenotypic Data by Genotype

(show or hide all phenotypic details)

Genotype

Allelic Composition

Genetic Background

ht1 Disease Model

Mecp2^tm1Hzo/Mecp2⁺

129S7/SvEvBrd-Mecp2^tm1Hzo

ot2 Disease Model

Mecp2^tm1Hzo/Y

129S7/SvEvBrd-Mecp2^tm1Hzo

ot3 Disease Model

Mecp2^tm1Hzo/Y

involves: 129S7/SvEvBrd * C57BL/6J

life span/agingpremature death (J:78009)

most survive to at least one year of age, however about 10% die after 10 months of age

behavior/neurologicalincreased anxiety-related response (J:78009)

amount of exploratory behavior in the center of the open field does not change during testing like in wild-type mice which increase activity in the center space over time, likely reflecting heightened anxiety

abnormal motor capabilities/coordination/movement (J:78009)

abnormal involuntary movement (J:78009)

mutants rapidly and repetitively move their forelimbs, often bringing them together and sometimes holding them together for several seconds

tremors (J:78009)

develop subtle tremors at around 6 weeks of age that worsen with age and are visibly apparent by 4 months of age

impaired coordination (J:78009)

young mice perform well on motor function tests but become deficient as they age

exhibit a small impairment in the ability to stay on a modified rotarod (covered with duct tape to eliminate the grips), however do not exhibit defects in forepaw grip strength

in a vertical pole test, mutants fall off the pole more readily than wild-type

in a wire suspension test, mutants drop earlier than wild-type

on a thin horizontal wooden dowel, mutants rapidly lose balance and fall off the dowel

abnormal locomotor activity (J:78009)

mutants rapidly and repetitively move their forelimbs, often bringing them together and sometimes holding them together for several seconds

decreased vertical activity (J:78009)

although overall level of rearing is not significantly lower, males rear less during the last 10 min interval of testing

hypoactivity (J:78009)

travel shorter distances and spend less time walking in the open-field test

show normal activity during the first 10 min interval but reduced activity during the second and third 10 min time intervals

abnormal social investigation (J:78009)

in a tube test for social interaction, wild-type mice typically retreated when confronted with mutants, while mutants did not

total time that wild-type intruder mice spent interacting with mutants is significantly shorter than the time spent interacting with wild-type mice

seizures (J:78009)

spontaneous behavioral myoclonic jerks and seizures are seen in some mice after 8 months of age

nervous systemseizures (J:78009)

spontaneous behavioral myoclonic jerks and seizures are seen in some mice after 8 months of age

cellularabnormal nucleus morphology (J:78009)

exhibit histone H3 hyperacetylation in the cerebellum, cerebral cortex, and spleen, indicating that chromatin architecture is abnormal

skeletonkyphosis (J:78009)

40% develop kyphosis after 5 months of age

skin/coat/nailsdisheveled coat (J:78009)

after 8 months of age, fur is noticeably more disheveled

greasy coat (J:78009)

after 8 months of age, fur is noticeably more oily

Mouse Models of Human Disease	Note	Ref(s)
Models with phenotypic similarity to human diseases associated with human MECP2.
Rett Syndrome; RTT		J:78009

Disease
models

Mouse Models of Human Disease	Note	Genotype			Ref(s)
Mouse Models of Human Disease	Note		Allelic Composition	Genetic Background	Ref(s)
Models with phenotypic similarity to human diseases associated with human MECP2.
Rett Syndrome; RTT OMIM ID: 312750		ot2	Mecp2^tm1Hzo/Y	129S7/SvEvBrd-Mecp2^tm1Hzo	J:78009
		ht1	Mecp2^tm1Hzo/Mecp2⁺	129S7/SvEvBrd-Mecp2^tm1Hzo	J:78009
		ot3	Mecp2^tm1Hzo/Y	involves: 129S7/SvEvBrd * C57BL/6J	J:78009

References

Original:	J:78009 Shahbazian M et al., "Mice with truncated MeCP2 recapitulate many Rett syndrome features and display hyperacetylation of histone H3." Neuron 2002 Jul 18;35(2):243-54
All:	10 reference(s)

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