Mice homozygous for this targeted mutation are viable and fertile and do not display any gross physical or behavioral abnormalities. Hepatocytes are completely devoid of keratin filaments, but desmosomes are formed and maintained. At 18 months of age, mice consistently show a distinctive liver pathology with abnormal hepatocytes containing K8 (KRT8)-positive aggregates (Mallory bodies). No KRT18 protein is produced from the targeted gene, as determined by Western blot of liver tissue. This mutant mouse strain may be useful in studies pertaining to keratin 18 (Krt18) and its partner keratin 8 (Krt8) function in glandular tissues such as liver and pancreas.
A targeting vector was designed to replace exons 1 and part of 2 of the gene with an HPRT minigene driven by a mouse phosphoglycerate-kinase (PGK) promoter. Linearized vector was electroporated into 129P2/OlaHsd-derived HM-1 embryonic stem (ES) cells. Targeted clones were introduced to C57BL/6 or BALB/c blastocysts. The background of this strain is a mix of MF1, 129 and FVB. Upon arrival at The Jackson Laboratory, mutant mice were crossed to FVB/NJ inbred mice for at least one generation.
|Allele Name||targeted mutation 1, Thomas M Magin|
|Allele Type||Targeted (Null/Knockout)|
|Allele Synonym(s)||K18 null; K18-|
|Gene Symbol and Name||Krt18, keratin 18|
|Strain of Origin||129P2/OlaHsd-Hprtb-m3|
|Molecular Note||An HPRT minigene replaced most of exon 1, intron 1 and exon 2.|
|Mutations Made By|| |
Guozhong Tao, Stanford University
When maintained as a live colony, heterozygotes or homozygotes may be used for breeding.
When using the K18 KO mouse strain in a publication, please cite the originating article(s) and include JAX stock #007029 in your Materials and Methods section.