FVB.129P2(Cg)-Hlx^tm1Rph/J

Stock number: 008315
Research areas: Developmental Biology Research, Hematological Research, Immunology, Inflammation and Autoimmunity Research, Internal/Organ Research

Description

Mice homozygous for this Hlx targeted mutation have an embryonic or perinatal lethal phenotype, failing to develop past ED15.5 or dying at birth. Homozygotes exhibit defective fetal hematopoiesis with abnormal liver and gut development. Naive CD4 T cells from heterozygotes on the FVB/NJ background exhibit increased responsiveness to IL-4, resulting in differentiation of more Th2 cells. This mutant mouse strain may be useful in studies of liver and gastrointestinal development and T helper 2 cell differentiation.

Detailed description

Homozygous null mice have an embryonic lethal phenotype. Homozygous mice on the C57BL/6 and B6;129 mixed background fail to develop past embryonic days 15.5 due to impaired fetal hematopoiesis (anemia, hypoplastic and abnormal development of the liver, hypoplastic gut). Homozygous mice on the FVB/N background survive through embryonic day 18.5 and dead homozygote newborn pups are observed. Late gestation homozygous embryos on the FVB/N background are smaller than wild-type littermates, pale, hydropic (subcutaneous fluid ballooning skin), and have impaired neural crest cell and enteric neuron migration from the stomach to intestine. Mice that are heterozygous for the targeted mutation are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. Naive CD4 T cells from heterozygotes exhibit increased responsiveness to IL-4, resulting in differentiation of more Th2 cells. This mutant mouse strain may be useful in studies of liver and gastrointestinal development and T helper 2 cell differentiation.

Development

A targeting vector containing neomycin resistance and herpes simplex virus thymidine kinase genes was used to disrupt a portion of exon 4 encoding the homeobox. The construct was electroporated into 129P2/OlaHsd derived E14 embryonic stem (ES) cells. Correctly targeted ES cells were injected into (C57BL/6 x C57BL/10)F1 blastocysts. The resulting chimeric animals were interbred before being crossed to FVB mice, and then backcrossed to FVB/NJ for 10 generations.

Allele

Symbol: Hlx^tm1Rph
Name: targeted mutation 1, Richard P Harvey
MGI accession ID: MGI:2182089
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Hlx
Marker name: H2.0-like homeobox
Chromosome: 1
Strain of origin: 129P2/OlaHsd
Molecular note: A neomycin selection cassette replaced the sequence encoding the DNA-binding helix 3 of the homeodomain.