FVB.129P2-Bmi1^tm1Brn/MvlJ

Stock number: 024584
Product name: bmi-1-
Research areas: Developmental Biology Research, Internal/Organ Research, Neurobiology Research

Description

Bmi1 KO mice may be useful for studying morphogenesis and hematopoiesis during embryonic development.

Detailed description

A hygromycin cassette replaces replace the ATG start codon, the zinc finger motif, and part of the helix-turn-helix motif of the Bmi1 polycomb ring finger oncogene (Bmi1) gene, abolishing gene function. BMI1 is a transcriptional regulator that is involved in chromatin remodeling and modification of histones. BMI1 is expressed in most tissues, but high expression is found in the thymus, heart, brain, and testes, and also in embryonic stem (ES) cells during embryonic development and in placenta. Heterozygous mice are viable and fertile. Half of homozygous mice die within 3 days of birth. The remaining survivors are significantly smaller than control littermates and die at an age varying from 3 to 20 weeks due to reoccurring illnesses such as pneumonia, anemia, and intestinal infections. Homozygotes do not express BMI1 in spleen, testis, liver, or brain. Homozygous mice exhibit a progressive decrease in the number of hematopoietic cells and an impaired proliferative response of these cells to mitogens. They also display neurological abnormalities manifested by an ataxic gait and sporadic seizures. Homozygous mice have abnormal skeletal transformation affecting the anteroposterior axis of the skeleton. Some of the skeletal transformations are also present in heterozygous mice.

Development

A targeting vector was designed to replace the ATG start codon, the zinc finger motif, and part of the helix-turn-helix motif of the Bmi1 polycomb ring finger oncogene (Bmi1) gene with a hygromycin resistance (hygro) cassette. The construct was electroporated into 129P2/OlaHsd-derived E14 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts and the resulting chimeric males were bred to 129/Ola females. These mice were backcrossed for more than 60 generations to FVB/N background. Upon arrival at The Jackson Laboratory, mice were bred to FVB/NJ (Stock No. 001800) for at least one generation to establish the colony.

Allele

Symbol: Bmi1^tm1Brn
Name: targeted mutation 1, Anton Berns
MGI accession ID: MGI:1857632
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Bmi1
Marker name: Bmi1 polycomb ring finger oncogene
Chromosome: 2
Strain of origin: 129P2/OlaHsd
Molecular note: The sequences encoding the ATG start codon, the zinc finger motif, and part of the helix-turn-helix motif were replaced either with a hygromycin-resistance cassette or one that conveyed neomycin-resistance.