B6.Cg-Ing5^tm1.2Avo/TthoJ

Stock number: 039502
Product name: Ing5^fl
Research areas: Cardiovascular Research, Cell Biology Research, Developmental Biology Research, Hematological Research, Internal/Organ Research, Research Tools

Description

Ing5^fl mice have loxP sites flanking exons 3-5 of the Ing5 gene. These mice may be useful when studying the role of ING5 during fetal development of the hematopoietic system.

Detailed description

Ing5^fl mice have loxP sites flanking exons 3-5, encoding part of the N-terminal inhibitor of growth (ING) domain and the nuclear localization signal, of the inhibitor of growth family, member 5 (Ing5) gene. Ing5 encodes a tumor suppressor protein that inhibits cell growth and induces apoptosis. It is part of the HBO1 complex, which specifically mediates acetylation of histone 3 lysine 14 (H3K14), and is involved in DNA replication, gene transcription, proliferation, cell fate commitment. With KAT6B and KAT6A, ING5 cooperatively promotes transcription of genes regulating hematopoiesis.

Homozygous Ing5^fl mice are viable and fertile. When bred to CMV-cre transgenic mice (Stock No. 006054), with widespread deletion of Ing5, only a third of expected Ing5^-/- pups were present at weaning from heterozygous matings. No Ing5 RNA was detected in Ing5^-/- embryos, and they exhibit decreased fetal liver cellularity, decreased numbers of hematopoietic stem cells, and perturbed erythropoiesis compared to wild-type control mice. Ing5^-/- embryos exhibit severely cytopenic and hypoplastic spleens and have cardiac ventricular septal defects. Competitive transplantation experiments using fetal liver hematopoietic cells show no defect in long-term repopulating capacity of stem cells lacking ING5. Surviving Ing5^-/- mice were normal and fertile.

These mice may be useful when studying the role of ING5 during fetal development of the hematopoietic system.

The donating investigator has deposited a group of floxed strains that are useful for studying development of hematopoietic stem cells and the regulation of hematopoiesis:
Kat6a^fl [Moz3^lox] (Stock No. 039488)
Phf6^lox (Stock No. 039489)
Kat7^lox [Hbo1^lox] (Stock No. 039490)
Ing5^fl (Stock No. 039502)
Ing4^fl (Stock No. 039503)

Development

The Ing5^fl targeting vector was designed to insert loxP sites flanking exons 3-5, encoding part of the N-terminal ING domain and the nuclear localization signal, of the inhibitor of growth family, member 5 (Ing5) gene, and a frt-flanked neomycin resistance (neo) cassette was also inserted downstream of the 5' loxP site. The construct was electroporated into B6.Cg-Thy1^a-derived Bruce4 embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts and the chimeric mice were bred to ROSA26::FLPe mice (Stock No. 009086) to remove the neo cassette. Resulting Ing5^fl offspring were bred to C57BL/6J mice (Stock No. 000664) for at least 10 generations by the donating laboratory. Upon arrival at The Jackson Laboratory, sperm was cryopreserved. To establish our live colony, an aliquot of frozen sperm was used to fertilize C57BL/6J oocytes.

Allele

Symbol: Ing5^tm1.2Avo
Name: targeted mutation 1.2, Anne K Voss
MGI accession ID: MGI:7643725
Generation method: Targeted
Attributes: Conditional ready (e.g. floxed)
Synonyms: Ing5^fl
Marker symbol: Ing5
Marker name: inhibitor of growth family, member 5
Marker synonyms: 1700027H23Rik; 1810018M11Rik; p28ING5
Chromosome: 1
Strain of origin: B6.Cg-Thy1^a
Molecular note: The targeting vector was designed to insert loxP sites flanking exons 3-5, encoding part of the N-terminal ING domain and the nuclear localization signal, of the inhibitor of growth family, member 5 (Ing5) gene, and a frt-flanked neomycin resistance (neo) cassette was also inserted downstream of the 5' loxP site. FLPe-mediated recombination removed the neo cassette.