These PLCBeta4 null mice exhibit impaired visual processing, ataxia, tremors, Purkinje cell fiber abnormalities and are less susceptible to inflammatory pain. This mutant mouse strain may be useful in studies of photoreceptor transduction, inflammatory pain.
Melvin Simon, University of California, San Diego
Phospholipase C, beta 4, is involved in retina signal transduction, specifically the photocascade in the rod outer segment. Mutations in human PLCB4 are a cause of auriculo-condylar syndrome-2.
Mice that are homozygous for this Plcb4 targeted mutation are viable and fertile, but have shortened lifespans. The Donating Investigator reports that homozygotes are difficult to breed. No gene product (protein) is detected by Western blot analysis of retinal tissue and cerebellum or by immunohistochemical analysis of brain tissue from homozygotes.
Homozygotes exhibit abnormal electroretinograms (reduced a-wave
and b-wave) and impaired visual processing, as assessed by a shuttle box test. At approximately 3 weeks of age, homozygotes are ataxic with uncoordinated locomotion, body swaying and intention tremors. Histological examination of rostral cerebellum from homozygotes reveals more Purkinje cells remain multiply-innervated when compared to controls.
Although the inflammatory response to a formalin nociceptive test is similar to that seen in controls, the formalin-induced inflammatory pain behavior is reduced in homozygous mice.
The Donating Investigator reports that homozygotes are difficult to breed, and have a lifespan of approximately 4 to 6 months
A targeting vector containing a NEO cassette was used to disrupt the exon encoding the catalytic domain, the X box. The construct was electroporated into 129S1/Sv-Oca2+ Tyr+ Kitl+ derived CJ7 embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts. The resulting chimeric animals were crossed to C57BL/6 mice, and then backcrossed to C57BL/6 for 5 generations.
Upon arrival at The Jackson Laboratory, the mice were crossed to C57BL/6J (Stock No. 000664) at least once to establish the colony.
|Allele Name||targeted mutation 1, Dianqing Wu|
|Allele Type||Targeted (Null/Knockout)|
|Gene Symbol and Name||Plcb4, phospholipase C, beta 4|
|Strain of Origin||129S1/Sv-Oca2+ Tyr+ Kitl+|
|Molecular Note||The exon encoding the X box was disrupted by the insertion of a neomycin selection cassette. Encoded protein was undetected in retinal extracts and brain sections via Western blot analysis and immunohistochemical staining, respectively.|
|Mutations Made By|| |
Estelle Wall, University of California, San Diego
When maintaining a live colony, these mice can be bred as heterozygotes. The Donating Investigator reports homozygotes are difficult to breed, and have a lifespan of approximately 4 to 6 months.
When using the B6.129S1-Plcb4tm1Dwu/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #019024 in your Materials and Methods section.