FVB.129P2(B6)-Kdm5b^{Gt(RRO123)Byg}/KaelJ

Stock number: 027473
Product name: Jarid1b KO
Research areas: Cancer Research, Cell Biology Research, Developmental Biology Research, Endocrine Deficiency Research, Reproductive Biology Research, Research Tools

Description

These mice carry a β-geo genetrap/knockout mutation located in intron 2 of the mouse Kdm5b (Jarid1b) gene. Unlike other knockouts of this gene, the majority of homozygotes from this line are viable beyond embryonic and neonatal stages.

Detailed description

Histone demethylase JARID1B (Kdm5b, lysine (K)-specific demethylase 5B) promotes luminal lineage transcription programs in the mammary gland and fine-tunes systemic estrogen levels. It is overexpressed in HER2+ breast cancer and many breast cancer cell lines, making it a potential target for treatment.

These mice carry a β-geo genetrap/knockout mutation located in intron 2 of the mouse Kdm5b gene that creates a premature termination of the protein before the AT-rich interactive domain (ARID). Western blot analysis using an antibody against the C terminus shows that full-length protein is undetectable. β-geo can be used effectively for lacZ staining of cells normally expressing JARID1B.

Unlike other knockouts of this gene, the majority of homozygotes from this line are viable beyond embryonic and neonatal stages. Some animals die between 3-6 months of age for undetermined reasons. Others can live up to 2 years. Mice exhibit decreased body weight, premature mortality, decreased female fertility, lower uterine weight, and delayed mammary gland development. Serum estrogen levels are decreased and reduced mammary epithelial cell proliferation in observed in early puberty.

Ex vivo cells derived from the mammary glands of homozygotes exhibit diminished expression of key regulators of mammary gland morphogenesis and luminal lineage specification along with increased expression of a mammary stem cell signature.

Development

A gene trap vector containing a splice-acceptor sequence upstream of β-geo (a fusion of β-galactosidase and neomycin phosphotransferase II) was introduced to intron 2 of the gene. This mutation was created in 129P2/OlaHsd-derived E14TG2a.4 embryonic stem (ES) cells. Correctly-targeted ES cells were injected into C57BL/6 blastocysts, and chimeric mice were bred with C57BL/6 mice. These mice were backcrossed to C57BL/6 for at least 7 generations, then backcrossed to FVB for 10 generations by the donating laboratory.

Allele

Symbol: Kdm5b^{Gt(RRO123)Byg}
Name: gene trap RRO123, BayGenomics
MGI accession ID: MGI:4329395
Generation method: Gene trapped
Attributes: Reporter; Null/Knockout
Marker symbol: Kdm5b
Marker name: lysine (K)-specific demethylase 5B
Chromosome: 1
Strain of origin: 129P2/OlaHsd
Expressed genes: Bgeo,fusion of beta-galactosidase and neomycin phosphotransferase genes,E. coli
Site of expression: lacZ can be detected in cells normally expressing Kdm5b in the mammary gland.
Molecular note: A gene trap vector containing a splice-acceptor sequence upstream of beta-geo (a fusion of beta-galactosidase and neomycin phosphotransferase II) was introduced to intron 2 of the gene, resulting in premature termination of the protein before the AT-rich interactive domain (ARID). Western blot analysis using an antibody against the C terminus shows that full-length protein is undetectable.
General note: E14TG2a.4 embryonic stem cells