Parvalbumin knock-out mice exhibit prolonged contraction-relaxation cycle in fast-twitch muscle as well as multiple behavioral phenotypes associated with autism spectrum disorders.
Beat Schwaller, University of Fribourg
Pvalb (parvalbumin) encodes a high affinity calcium ion-binding protein that is expressed at high levels in fast contracting muscles and, to different extents, in brain and several endocrine tissues. During a fast-twitch in tibialis anterior muscles, the decay of the intracellular calcium concentration is slower compared with wild-type mice. This leads to a prolongation of the time required to attain peak twitch tension and to slower relaxation kinetics. In analogy, absence of parvalbumin increases facilitation of synaptic transmission, since the presence of parvalbumin slows down build-up of residual calcium in presynaptic terminals leading to facilitation. In addition, loss of parvalbumin results in multiple phenotypes associated with autism spectrum disorders including: abnormal social interactions, impaired communication, repetitive and stereotypic behaviors, reduced pain sensitivity, reduced startle response and increased seizure susceptibility. MRI analysis reveals transient cortical hypertrophy and cerebellar hypoplasia in the brains of homozygotes. Mice homozygous for this knockout allele are viable and fertile.
A targeting vector containing neomycin resistance and herpes simplex virus thymidine kinase genes was used to disrupt exons 2 through 4. The construct was electroporated into 129P2/OlaHsd-derived E14 embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts. The resulting chimeric animals were bred to C57BL/6J and offspring were backcrossed to C57BL/6J for 10 generations by the donating lab (see SNP note below). Upon arrival, mice were bred to C57BL/6J for at least 1 generation to establish the colony.
A 32 SNP (single nucleotide polymorphism) panel analysis, with 27 markers covering all 19 chromosomes and the X chromosome, as well as 5 markers that distinguish between the C57BL/6J and C57BL/6N substrains, was performed on the rederived living colony at The Jackson Laboratory Repository. While 26 of the 27 markers throughout the genome suggested a C57BL/6 genetic background, 3 of 5 markers that determine C57BL/6J from C57BL/6N were found to be segregating. These data suggest the mice sent to The Jackson Laboratory Repository were on a mixed C57BL/6J ; C57BL/6N genetic background.
|Allele Name||targeted mutation 1, Beat Schwaller|
|Allele Type||Targeted (Null/Knockout)|
|Gene Symbol and Name||Pvalb, parvalbumin|
|Strain of Origin||129P2/OlaHsd|
|Molecular Note||A fragment encompassing a portion of exon 2 and all of exons 3 and 4 was replaced with a PGK-neo cassette inserted by homologous recombination. Approximately 85% (nt 25 to 304) of the coding region was deleted. No protein was detected by Western blot analysis of various skelelal muscle tissue samples obtained from homozygous mutant mice.|
While maintaining a live colony, these mice are bred as homozygotes.
When using the PV- mouse strain in a publication, please cite the originating article(s) and include JAX stock #027503 in your Materials and Methods section.