These Ppt1 knock-out mice exhibit progressive hind limb paralysis, reduced body weight, abnormal clasping behavior, and early mortality.
Sandra Hofmann, Center at Dallas
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 strain represents a model that may be useful in studies of neuronal ceroid lipofuscinoses, including infantile Batten disease.
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.
|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|| |
This strain originated on a 129S6 background. Heterozygotes were bred to C57BL/6 mice and then intercrossed to produce homozygotes. The strain is maintained on a B6;129S6 background.
When using the PPT1 KO mouse strain in a publication, please cite the originating article(s) and include JAX stock #004313 in your Materials and Methods section.