Strain Detail Sheet

Phenotype:
Hemizygous males and homozygous females develop disease (gait ataxia, frequent obesity) around 5 weeks and die as young adults (8 to 12 weeks). Heterozygous females stay healthy for at least 4 months. Mutant brains showed substantial reduction in both weight and neuronal cell size, but no obvious structural defects or signs of neurodegeneration.

Mammalian Phenotype Terms:(provided by MGI)      Extend all MPTs
      assigned by genotype

The following phenotype information may relate to one or more alleles on a genetic background differing from this MMRRC strain.

Mecp2^tm1.1Jae/Mecp2⁺

        involves: 129S4/SvJae * BALB/c * C57BL/6

• behavior/neurological phenotype
  • ataxia (MGI Ref ID J:67909)
    • females appear normal for the first 4 months but show ataxic gait at later ages
  • hypoactivity (MGI Ref ID J:67909)
    • females appear normal for the first 4 months but show hypoactivity at later ages
• growth/size phenotype
  • increased susceptibility to age related obesity (MGI Ref ID J:67909)
    • females appear normal for the first 4 months but gain weight at later ages

Mecp2^tm1.1Jae/Mecp2⁺

        involves: 129S4/SvJae * C57BL/6

• behavior/neurological phenotype
  • hypoactivity (MGI Ref ID J:89593)
• growth/size phenotype
  • decreased body weight (MGI Ref ID J:89593)
    • mutants are severely underweight from 4-5 weeks of age
• nervous system phenotype
  • decreased brain weight (MGI Ref ID J:89593)
    • 8 - 13 week old mutants display a 14-18% reduction in brain weight

Mecp2^tm1.1Jae/-

        involves: 129S4/SvJae * BALB/c * C57BL/6

• mortality/aging
  • premature death (MGI Ref ID J:67909)
    • most die at about 10 weeks of age without obvious correlation between physical deterioration and time of death
• behavior/neurological phenotype
  • abnormal behavior (MGI Ref ID J:67909)
    • appear healthy for the first few weeks of age but develop abnormal behavior, such as nervousness, at 5 weeks of age
    • abnormal pilomotor reflex (MGI Ref ID J:67909)
      • seen at 5 weeks of age
    • hypoactivity (MGI Ref ID J:67909)
      • seen at late stages of disease
    • tremors (MGI Ref ID J:67909)
      • exhibit body trembling at 5 weeks of age
      • at late stages of disease, mutants tremble when handled
• nervous system phenotype
  • abnormal hippocampus CA2 region morphology (MGI Ref ID J:67909)
    • neurons in the CA2 region are 15-25% smaller than in controls at 9 weeks of age
  • abnormal neuron morphology (MGI Ref ID J:67909)
    • cell bodies and nuclei or neurons in sections of hippocampus, cerebral cortex, and cerebellum are smaller in size and more densely packed
  • decreased brain size (MGI Ref ID J:67909)
    • decreased brain weight (MGI Ref ID J:67909)
• growth/siz e phenotype
  • cachexia (MGI Ref ID J:67909)
    • most exhibit signs of physical deterioration by 8 weeks of age and often begin to lose weight at late stages of disease
  • obese (MGI Ref ID J:67909)
    • 8 of 17 become overweight and obese at 40-60 days of age
• homeostasis/metabolism phenotype
  • abnormal body temperature (MGI Ref ID J:67909)
    • frequently display cold extremities
• respiratory system phenotype
  • abnormal respiration (MGI Ref ID J:67909)
    • occasionally show heavy breathing at 5 weeks of age

Founder genetic background: 129/Sv

Strain genetic background: Mixed background

Strain Development:
Independent Mecp22lox ES cells derived from B6129F1 ES cell line were injected into BALB/c host blastocysts to generate chimeras, which were subsequently crossed with BALB/c mice to derive mice bearing a germline transmitted Mecp22lox allele.

The 1Lox mice were generated from 1Lox/y ES cells (not from crossing the 2Lox animals to a mouse expressing Cre). The loop out was done in cultured (2Lox/Y) ES cells by transient transfection of a Cre expressing plasmid. The ES cell clones were screened by southern to find out the ones that successfully recombined to a 1Lox allele and these were used to generate 1Lox animals..

Donor: Dr. Rudolf Jaenisch, Whitehead Institute, MIT

Primary Reference:

Chen RZ, Akbarian S, Tudor M, Jaenisch R. Deficiency of methyl-CpG binding protein-2 in CNS neurons results in a Rett-like phenotype in mice. Nat. Genet. (2001) 27, 327-331 (Medline: 11242118)

Jugloff DG, Logan R, Eubanks JH. Breeding and maintenance of an Mecp2-deficient mouse model of Rett syndrome. J Neurosci Methods. 2006 Jan 23; [Epub ahead of print] (Medline PMID: 16439027)

Coat color: Unknown

Other:

MMRRC Breeding System: Intrastrain

Breeding Scheme(s):

• Heterozygous Females x Mecp2^+/Y Male Littermates
• Heterozygous Females x Wildtype Males (e.g., C57BL/6J)

Generation: N3 As of: 01/2003

Overall Breeding Performance: Good

Viability and Fertility	Female	Male
Homozygotes are viable:	No	No
Homozygotes are fertile:	No	No
Heterozygotes are fertile:	Yes	Yes*
* Hemizygous Males die by 3 months
Age Reproductive Decline:	36 weeks	Unknown

Heterzygous females become obese and ill at an early age (approximately 4 months). Hemizygous males have delayed reproductive maturity (approximately 10 weeks), become ill as early as 5 weeks and die by 12 weeks.

Additional charges may apply for any special requests. Shipping costs are in addition to the basic distribution/resuscitation fees. Information on shipping costs and any additional charges will be provided by the supplying MMRRC facility.

Click button to Request this one strain. (Use the MMRRC Catalog Search to request more than one strain.) Request this Strain
MMRRC Item # Description	Distribution Fee/unit (US $)	Units	Notes
000011-UCD-HET-F Heterozygous female 000011-UCD-WT-M Wild type male	$218.00 Non-Profit $571.00 For-Profit	EA	The mmrrc@ucdavis.edu may assess additional fees for any special requests (e.g., specific age or weight of mice, etc.).
000011-UCD-RESUS Litter recovered from cryo-archive	$2,022.00 Non-Profit $4,109.00 For-Profit	Litter	Recovered litter1; additional fees for any special requests.
000011-UCD-SPERM Cryo-preserved spermatozoa	$437.00 Non-Profit $817.00 For-Profit	Aliquot	Approximate quantity.2
000011-UCD-EMBRYO Cryo-preserved embryos	$1,038.00 Non-Profit $2,621.00 For-Profit	Aliquot	Approximate quantity3: 20-40 embryos / aliquot

¹ The distribution fee covers the expense of resuscitating mice from the cryo-archive; you will receive the resulting litter. The litter will contain at minimum one breedable mutant carrier; the actual number of animals and the gender and genotype ratios will vary. (Typically, multiple breeder pairs can be established from the recovered litter.) Prior to shipment, the MMRRC will provide information about the animals recovered. If you anticipate or find that you need to request specific genotypes, genders or quantities of mice in excess of what is likely from a resuscitated litter, you may discuss available options and pricing with the supplying MMRRC facility.

² An aliquot contains sufficient material (volume and concentration) for at least two IVF or several artificial inseminations (based on our procedures). The MMRRC makes no guarantee concerning success of these procedures when performed outside the MMRRC facilities.

³ An aliquot contains a sufficient number of embryos (in one or more vials and based on the transfer success rate of the MMRRC facility) to transfer to at least two recipients. The MMRRC makes no guarantee concerning embryo transfer success experienced in the recipient investigator's laboratory. Neither gender nor genotype ratios are guaranteed.