B6.129-Foxo6^tm1Abru/J

Stock number: 021347

Description

In this strain a NEO cassette replaces exon 1 of the Foxo6 (forkhead box O6) gene. These mice exhibit impaired memory consolidation and abnormal hippocampal neuron morphology.

Detailed description

The transcription factor forkhead box O6 is expressed primarily in the central nervous system (predominantly in the hippocampal CA1 and CA3 regions), and is negatively regulated by the insulin and insulin-like growth factor (IGF) signaling pathway. These mice carry a targeted mutation of the mouse Foxo6, forkhead box O6, gene in which a NEO cassette replaced exon 1. Mice that are homozygous for this targeted mutation are viable and fertile, but have smaller litter sizes compared to wildtype controls. No full-length gene product (mRNA or protein) is detected by Western blot analysis of the anterior brain, cortex, hippocampus and testes or by RT-PCR analysis of hippocampus. Homozygotes exhibit impaired memory consolidation, as indicated by contextual memory tests. Reduced dendritic spine density of hippocampal neurons is observed in cultured hippocampal neurons and dendritic spine length is also increased in the CA1 region of homozygous mice. During backcrossing, the Y chromosome may not have been fixed to the C57BL/6J genetic background.

In an attempt to offer alleles on well-characterized or multiple genetic backgrounds, alleles are frequently moved to a genetic background different from that on which an allele was first characterized. This is the case for the strain above. It should be noted that the phenotype could vary from that originally described. We will modify the strain description if necessary as published results become available.

Development

A targeting vector designed by Dr. Anne Brunet (Stanford University School of Medicine) containing a NEO cassette was used to disrupt exon 1. The construct was electroporated into 129 derived R1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts. The resulting chimeric animals were crossed to C57BL/6 mice. The mice were then backcrossed to C57BL/6J for 11 generations. During backcrossing, the Y chromosome may not have been fixed to the C57BL/6J genetic background. Upon arrival at The Jackson Laboratory, the mice were crossed to C57BL/6J (Stock No. 000664) at least once to establish the colony.

Allele

Symbol: Foxo6^tm1Abru
Name: targeted mutation 1, Anne Brunet
MGI accession ID: MGI:5473578
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Foxo6
Marker name: forkhead box O6
Chromosome: 4
Strain of origin: (129X1/SvJ x 129S1/Sv)F1-Kitl⁺
Molecular note: A neo cassette replaced exon 1. Western blot analysis confirmed the absence of protein expression in the anterior brain, cortex and hippocampus.