B6.Cg-Phf6^tm1.1Avo/TthoJ

Stock number: 039489
Product name: Phf6^lox
Research areas: Cancer Research, Cell Biology Research, Developmental Biology Research, Hematological Research, Research Tools

Description

Phf6^lox mice have loxP sites flanking exons 4-5 of the X-linked Phf6 gene. These mice may be useful when studying the development of hematopoietic stem cells and the regulation of hematopoiesis and T-ALL.

Detailed description

Phf6^lox/lox mice have loxP sites flanking exons 4-5 of the X-linked PHD finger protein 6 (Phf6) gene. Also known as plant homeodomain finger 6, Phf6 encodes a nuclear protein involved in the transcription of genes regulating hematopoiesis. Mutations have been linked to the onset of intellectual disability and other neurological disorders as well as tumorigenesis. These mutations have been associated with the onset of T-cell acute lymphoblastic leukemia (T-ALL) and acute and chronic myeloid neoplasms.

Homozygous lox/lox females and hemizygous lox/Y males are viable and fertile. When bred to Tie2-cre transgenic mice (Stock No. 008863), deletion in hematopoietic and endothelial cells results in a modestly accelerated onset of spontaneous hematopoietic malignancy. Mice have reduced numbers of hematopoietic stem cells (HSCs) which display enhanced differentiation to WBCs compared with control HSCs, and increased numbers of heterogeneous progenitor cells. Also, bone marrow from Phf6^lox/Y;Tie2-Cre^Tg/+ donors display an increased and sustained hematopoietic reconstitution in serial transplantation experiments.

These mice may be useful when studying the development of hematopoietic stem cells and the regulation of hematopoiesis and T-ALL.

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 Phf6^lox targeting vector was designed to insert loxP sites flanking exons 4-5 of the X-linked PHD finger protein 6 (Phf6) gene, and a frt-flanked neomycin resistance (neo) cassette was also inserted between exon 5 and the 3' 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 Phf6^lox 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: Phf6^tm1.1Avo
Name: targeted mutation 1.1, Anne K Voss
MGI accession ID: MGI:6507034
Generation method: Targeted
Attributes: Conditional ready (e.g. floxed)
Synonyms: Phf6^lox
Marker symbol: Phf6
Marker name: PHD finger protein 6
Marker synonyms: 2700007B13Rik; 4931428F02Rik; BFLS; BORJ; CENP-31; mKIAA1823
Chromosome: X
Strain of origin: B6.Cg-Thy1^a
Molecular note: A loxP site was inserted upstream of exon 4 and an FRT-flanked neomycin phosphotransferase expression cassette followed by a second loxP site were inserted downstream of exon 5. The neomycin cassette was removed via Flp-mediated recombination leaving exons 4-5 floxed.