Strain Detail Sheet

Strain Name: B6;129S4-Mbd1^tm1Fhg/Mmucd

Stock Number: 029591-UCD

Other Names:

MBD1, B6;129S4-Mbd1^tm1Fhg/Mmcd

Gene Details: (provided by MGI)

Allele Symbol: Mbd1^tm1Fhg
Name: targeted mutation 1, Fred H Gage
Alteration at locus: Knockout

Genetic Alterations:
Generation of MBD1

Genotype Determination:

MMRRC's PCR

ES Cell Line: J1 derived from C57BL/6

Strain Description

Phenotype
Homozygous phenotype: Histological analysis indicated that MBD1-/- mice had no detectable developmental defects. Therefore, donor focused analysis on adult mice. Adult MBD1-/- mice appear healthy and fertile, with a normal life span. Donor performed a battery of neurological tests and found no significant defects in adult MBD1-/- mice. However, the animal showed deficits in adult neurogenesis and hippocampal function (described in Zhao, X et al PNAS 2003).

Heterozygous phenotype: Not applicable

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.

Mbd1^tm1Fhg/Mbd1^tm1Fhg

129S4/SvJae-Mbd1<tm1Fhg>

nervous system phenotype
- abnormal dentate gyrus morphology (MGI Ref ID J:83613)
  - adult homozygotes show an 8.1% reduction in the cell density of the dentate gyrus relative to wild-type littermates
- abnormal hippocampus development (MGI Ref ID J:83613)
  - adult homozygotes display a significantly reduction in hippocampal neurogenesis, with little change in astrocytogenesis relative to wild-type littermates
- abnormal long term potentiation (MGI Ref ID J:83613)
  - homozygotes display a severe reduction of LTP in the detate gyrus of the hippocampus relative to wild-type littermates
  - in contrast, LTP in the CA1 region of the hippocampus remains relatively unaffected
- abnormal neuron differentiation (MGI Ref ID J:83613)
  - in culture, adult neural stem cells (ANCs) isolated from homozygous mutant brains differentiate into 41% fewer type III beta-tubulin-positive (TuJI⁺) neurons than wild-type cells, indicating reduced neuronal differentiation; however, no significant difference in the % of differentiated astrocytes (GFAP⁺) is observed
  - in vivo, adult homozygotes show a 54.9% decrease in the number of BrdUrd⁺ cells and a 42.9% decrease in the percentage of new neurons in the dentate gyrus indicating an overall 74.3% decrease in the number of new neurons relative to wild-type littermates
  - in contrast, the percentages of new astrocytes (GFAP⁺ and BrdUrd⁺) and cells with unknown phenotype (BrdUrd⁺, NeuN^-, and GFAP^-) are increased in the dentate gyrus of mutant mice relative to wild-type controls
- decreased brain weight (MGI Ref ID J:83613)
  - adult mutant forebrains weigh 15.2% less than those of wild-type littermates
  - however, no significant difference in body weight between adult wild-type and mutant mice is observed
behavior/neurological phenotype
- behavior/neurological phenotype (MGI Ref ID J:83613)
  - adult homozygotes are healthy and display no significant deficits in motor coordination or locomotor activity, as determined in the rotarod test and open field test
  - abnormal spatial learning (MGI Ref ID J:83613)
    - in the Morris water maze test, adult homozygotes require a significantly longer time than wild-type mice to locate a hidden platform, even after 9 days of training
    - upon removal of the platform, homozygotes spend more time in the start (opposite) quadrant searching for the platform, whereas wild-type mice spend more time in the target quadrant
cellular phenotype
- aneuploidy (MGI Ref ID J:83613)
  - analysis of prometaphase/metaphase spreads indicated that mutant ANCs show a significantly higher aneuploidy than wild-type ANCs (46% vs 21.3%, respectively)
  - unlike most wild-type aneuploid ANCs which typically lose chromosomes, the majority of mutant aneuploid ANCs (67.6%) are shown to gain chromosomes
  - 9 of 16 mutant aneuploid ANCs cells analyzed by SKY were shown to gain chromosome 10 whereas none of the 11 aneuploid wild-type cells gained chromosome 10
- chromosomal instability (MGI Ref ID J:83613)
  - mutant ANCs display a small but significant increase of endogenous viral (IAP) expression at both the mRNA (2.8-fold) and protein (5.4-fold) level relative to wild-type ANCs. suggesting increased genomic instability
  - treatment with trichostatin A (TSA), a histone deacetylase inhibitor, caused a significantly higher increase of IAP expression in mutant ANCs (3-fold) than in wild-type cells (0.37-fold)
  - however, no significant differences in the methylation status of IAP-LTR or in the global DNA methylation level were observed between mutant and wild-type ANCs
  - chromosome breakage (MGI Ref ID J:83613)
    - 3 of 29 mutant aneuploid ANCs, but none of 30 wild-type prometaphase/metaphase cells, analyzed by SKY were shown to have gained a fragment of chromosome 2, suggesting a possible chromosomal breakage
    - however, no chromosomal translocation was detected among the cells analyzed

Founder genetic background: 129

Strain genetic background: C57BL/6

Strain Development: Females MBD1+/- were crossed to male C57BL/6

Suggested Control Mice:

Wildtype littermates

Research Applications

Apoptosis
Cell Biology
Developmental Biology
Metabolism
Models for Human Disease
Neurobiology

Strain Origin

Donor: Fred H Gage, Ph.D., The Salk Institute

Primary Reference:

Zhao X, Ueba T, Christie BR, Barkho B, McConnell MJ, Nakashima K, Lein ES, Eadie BD, Willhoite AR, Muotri AR, Summers RG, Chun J, Lee KF, Gage FH. Mice lacking methyl-CpG binding protein 1 have deficits in adult neurogenesis and hippocampal function. Proc Natl Acad Sci U S A. 2003 May 27;100(11):6777-82. Epub 2003 May 14. (Medline PMID: 12748381)

Special Considerations

According to donor, female +/- with male +/- gives the best results

Health Status Report

Mice recovered from a cryo-archive will have health surveillance performed on recipient females. Health reports will be provided prior to shipment. If you require additional health status information, please email mmrrc@ucdavis.edu.

Order Request Information

Availability Level:

Limited quantities of breeder mice (recovered litter) are available from a cryoarchive; recovered litter usually available to ship in 3 to 4 months.

Conditions of Distribution:

Distribution of this strain requires submission of the MMRRC Conditions of Use (COU). A link to the COU web form will be provided via email after an order has been placed; the form should be completed then or the email forwarded to your institutional official for completion.

Fees:

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.)

MMRRC Item #	Description

Distribution
Fee/unit (US $)

Units

Notes

029591-UCD-RESUS

Litter recovered from cryo-archive

$2,022.00 / $4,109.00

Non-Profit / For-Profit

Litter

Recovered litter¹; additional fees for any special requests.

029591-UCD-SPERM

Cryo-preserved spermatozoa

$437.00 / $817.00

Non-Profit / For-Profit

Aliquot

Approximate quantity.²

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 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 is one straw or vial with sufficient sperm to recover at least one litter of mice, as per provided protocols, when performed at the MMRRC facility. The MMRRC makes no guarantee concerning the 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.

To request material from the MMRRC: Please fill out our on-line request form (accessible from the catalog search results page, or click the "Request this Strain" button above). If you have questions or need assistance completing this form, you may call Customer Service at (800) 910-2291 (in USA or Canada) or (530) 757-5710 (international calls). Before you call, please have with you: the MMRRC item number, quantity needed, Bill-to and Ship-to contact information.