B6.129P2-Akna^tm1Mak/J

Stock number: 029251
Product name: AKNA KO
Research areas: Developmental Biology Research, Hematological Research, Immunology, Inflammation and Autoimmunity Research, Research Tools

Description

This Akna knockout strain has exons 19 through 21 deleted and may be useful in studies of secondary immune response.

Detailed description

The targeted Akna gene encodes a transcription factor that upregulates CD40 receptor expression and is involved in secondary immune response. A mutation in this gene has been associated with an increased risk of cervical cancer. These knock-out mice carry a mutation in which a PGK-neo cassette replaced exons 19 through 21, which encode putative C-terminus AT-hook-like motif (ALM) sequence. A truncated gene product (mRNA) of the theorectical ALM sequence is detected by qRT-PCR analysis.

Homozygous neonates are smaller than wildtype controls and fail to thrive with most dying by postnatal day 10. Surviving homozygotes are very susceptible to inflammation induced by pathogen. Systemic inflammation with notable involvement of the lungs is detected in homozygous animals. Although alveolar morphology is normal at postnatal days 1 to 5, by postnatal day 7, homozygotes exhibit enlarged alveolar airspace. An increased number of neutrophils are found in bone marrow and peripheral blood. Mice that are heterozygous for the targeted mutation are viable and fertile. During backcrossing, the Y chromosome may not have been fixed to the C57BL/6 genetic background.

Development

A targeting vector containing a PGK-neo cassette was used to disrupt exons 19 through 21. The construct was electroporated into 129P2/OlaHsd derived E14K embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts. The resulting chimeric animals were tested for germline transmission. The mice were then backcrossed to C57BL/6 for 7 generations. Upon arrival, sperm was cryopreserved. To establish our live colony, an aliquot of frozen sperm was used to fertilize C57BL/6J oocytes (Stock No. 000664).

Allele

Symbol: Akna^tm1Mak
Name: targeted mutation 1, Tak Mak
MGI accession ID: MGI:5788727
Generation method: Targeted
Attributes: Hypomorph
Marker symbol: Akna
Marker name: AT-hook transcription factor
Chromosome: 4
Strain of origin: 129P2/OlaHsd
Molecular note: The targeting vector uses a PGK-neo cassette to disrupt exons 19 through 21. qRT-PCR analysis indicates that transcript expression is reduced but not completely abolished.