B6;129S6-Pdc^tm1Vya/J

Stock number: 025987
Research areas: Cell Biology Research, Neurobiology Research, Research Tools, Sensorineural Research

Description

Phosducin knockout (Pd-/-) mice may be useful in studying the role of phosducin in regulating the light sensitivity of synaptic transmission between photoreceptors (rods and cones) and "ON"-bipolar cells.

Detailed description

Phosducin is an abundant photoreceptor-specific protein. Mice homozygous for the phosducin knockout allele (Pd-/- or Pdc-/-) are viable and fertile with normal lifespan and no gross abnormalities. See breeding performance below.


Phosducin protein is completely absent in Pd-/- retinas. The rods and cones of Pd-/- mice have reduced levels of the photoreceptor-specific G protein transducin (20-30% and 40% reduction, respectively), and also exhibit impaired light-dependent transducin translocation. In addition, both rod- and cone-driven pathways behave as if persistently desensitized/illuminated, with cone-driven pathways affected most significantly. Specifically, homozygous mice have reduced bipolar cell response sensitivity in the dark and a lesser degree of response desensitization compared to wildtype.


The donating investigator reports the breeding performance of homozygous matings as averaging four pups per litter. Therefore, they suggest homozygous males be placed into breeding pairs at six weeks of age (and they have successful breeding for at least eight months); the age when homozygous females are bred is not as critical.

While other published phosducin knockout mice are reported to have stress-mediated hypertension (despite normal cardiac function and vascular reactivity) and elevated catecholamine turnover in the peripheral sympathetic system, such phenotypes have not been characterized for these Pd-/- mice (Stock No. 025987) to date (September 2014).

Development

The phosducin knockout allele (Pd- or Pdc-) was designed by Dr. Vadim Y. Arshavsky (Duke University Eye Center) to delete the promoter region and exon 1 of the phosducin gene (Pdc) on chromosome 1 and replace those sequences with a neomycin resistance cassette. The targeting vector was electroporated into 129S6/SvEvTac-derived IT2 embryonic stem (ES) cells. Correctly targeted ES cells were injected into recipient blastocysts. Chimeric mice were bred with C57BL/6J mice to establish the mutant colony. Mutant mice were bred together to make homozygotes. Homozygous (Pd-/-) mice were maintained on a mixed C57BL/6J and 129Sv background prior to sending agouti males to The Jackson Laboratory Repository in 2014. Upon arrival, sperm was cryopreserved. To generate the living colony, an aliquot of the frozen sperm was used to fertilize oocytes from C57BL/6J female mice (Stock No. 000664). Heterozygous mice were then bred to wildtype mice from the colony or with C57BL/6J inbred mice to maintain the colony.

Allele

Symbol: Pdc^tm1Vya
Name: targeted mutation 1, Vadim Y Arshavsky
MGI accession ID: MGI:3042204
Generation method: Targeted
Attributes: Null/Knockout
Synonyms: Pd^-
Marker symbol: Pdc
Marker name: phosducin
Marker synonyms: 33DPTP; MEKA; PHD; PhLOP; PhLP; Rpr1; Rpr-1
Chromosome: 1
Strain of origin: 129S6/SvEvTac
Molecular note: The promoter region and exon 1 were replaced with a neo cassette via homologous recombination. Western blot analysis showed the absence of protein in homozygous null mice.