This strain is currently unavailable due to replenishing of cryopreserved stocks. Interested customers who register interest will be contacted when the strain is again available.
These Ppt1 knock-out mice exhibit motor abnormalities, myoclonic jerking and seizures, and neuronal loss.
Brian Soper, The Jackson Laboratory
Mice that are homozygous for the targeted mutation are viable, normal in size and do not display any gross physical or behavioral abnormalities. No gene product (protein) is detected by immunoassay. Palmitoyl-protein thioesterase activity in the brain of the mutant is reduced to background levels. Although healthy at birth, by age four to five months, mutant mice display lack of grooming and an abnormal gait that progresses to hind limb paralysis. By six to eight months of age mutant mice have a low body weight and display an abnormal clasping behavior. Aggressive behavior results in fighting and dermatitis due to bite wounds. By seven months of age, mortality is 50% with very few mice surviving beyond ten months of age. Myoclonic jerks and seizures manifest at age three to four months. Strong rapid hind limb seizures ("popcorn" seizures) that propel mice several feet also occur. Brain size of the mutant mice is reduced. Histologically, mutant brains show neuronal loss and apoptosis in the hippocampus, cerebral cortex and cerebellum. Abundant autofluorescent storage material, termed granular osmiophilic deposits (GROD), seen under electron microscopic examination of mutant mouse brain tissue is indistinguishable from the GROD observed in human infantile neuronal ceroid lipofuscinosis. This mutant mouse strai n represents a model that may be useful in studies of neuronal ceroid lipofuscinoses, including infantile Batten disease.
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.
A targeting vector containing neomycin resistance and herpes simplex virus thymidine kinase genes was used to disrupt exon 9 of the targeted gene. The construct was electroporated into 129S6/SvEvTac derived SM1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6J blastocysts. The resulting male chimeric animals were backcrossed to C57BL/6J mice for 10 generations before arriving at The Jackson Laboratory.
|Allele Name||targeted mutation 1, Sandra L Hoffmann|
|Allele Type||Targeted (Null/Knockout)|
|Allele Synonym(s)||Cln1 mut; PPT1-; PPT1-KO|
|Gene Symbol and Name||Ppt1, palmitoyl-protein thioesterase 1|
|Strain of Origin||129S6/SvEvTac|
|Molecular Note||Part of exon 9 was replaced with a neomycin selection cassette containing an in frame stop codon that is predicted to cause premature termination of the protein. Nothern blot analysis on RNA derived from brain and other tissues of heterozygous and homozygous mice demonstrated that a truncated transcript is produced from this allele. However, western blot analysis and activity assays confirmed that no functional protein is expressed from this allele in homozygous mice.|
|Mutations Made By|| |
When maintaining a live colony, these mice can be bred as homozygotes. The Donating Investigator maintained the strain using a Heterozygote X Heterozygote breeding scheme and reports that homozygous animals will breed for only 3 or 4 litters.
When using the PPT1 KO mouse strain in a publication, please cite the originating article(s) and include JAX stock #006566 in your Materials and Methods section.