STOCK Proc^tm1Fjc/J

Stock number: 038808
Product name: PC^-
Research areas: Developmental Biology Research, Hematological Research

Description

PC^- mice carry a targeted knock-out of the mouse protein C (Proc) gene in which exons 2-9, containing the entire coding region, were replaced by a neomycin cassette. These mice have been useful in studies of coagulopathy.

Detailed description

PC^- mice carry a targeted knock-out of the mouse protein C (Proc) gene in which exons 2-9, containing the entire coding region, were replaced by a neomycin cassette. No detectable Proc mRNA is found in the liver of homozygotes, and no PROC protein activity is found in their plasma. Reduced levels of expression are found in heterozygotes.

Heterozygous matings yield the expected Mendelian distribution of genotypes. Homozygous pups obtained at embryonic day (E) 17.5 and at birth appear to develop normally macroscopically, but possess obvious signs of bleeding and thrombosis. Focal necrosis in the liver is observed. Bleeding is noted in the brain near sites of fibrin deposition. The severity of these pathologies is exaggerated in homozygous neonates. Most are born dead and the remainder expire within a few hours of birth. Plasma clottable fibrinogen is not detectable in coagulation assays in homozygous neonatal mice, suggestive of fibrinogen depletion and secondary consumptive coagulopathy. Plasma samples from homozygous E17.5 mice and neonatal mice do not clot at all, whereas heterozygous mice contained ~30–40% of the values found in homozygous mice at their corresponding stages of development.

While heterozygous mice do survive the early lethality, live to adulthood, and can be successfully employed in some disease models, the approximately 50% level of PROC in these mice is often too high to observe spontaneous phenotypes and is not reflective of symptomatic patients. For this reason, the donating laboratory also produced a model combining this targeted knock-out with a transgene to create animals expressing low levels of the protein (see Stock No. 038809).

Development

Exons 2-9, containing the entire coding region, were replaced by a neomycin cassette via homologous recombination in (129X1/SvJ x 129S1/Sv)F1- Kitl⁺-derived R1 embryonic stem (ES) cells. Resultant mice were backcrossed to C57BL/6J by the donating laboratory. The donating laboratory also notes CBA contributions to the genetic background.

Upon arrival at The Jackson Laboratory, sperm was cryopreserved. Cryorecovery/live colony development will involve C57BL/6J (Stock No. 000664).

Allele

Symbol: Proc^tm1Fjc
Name: targeted mutation 1, Francis J Castellino
MGI accession ID: MGI:2183063
Generation method: Targeted
Attributes: Null/Knockout
Synonyms: PC^-
Marker symbol: Proc
Marker name: protein C
Marker synonyms: APC; inactivator of coagulation factors Va, VIII; PC; PROC1; THPH3; THPH4
Chromosome: 18
Strain of origin: (129X1/SvJ x 129S1/Sv)F1-Kitl⁺
Molecular note: Exons 2 through 9, containing the entire coding region, were deleted by the insertion of a neomycin selection cassette. Northern blot analysis showed that transcript encoded by the endogenous allele was absent in homozygous mutant embryos. Assays of plasma obtained from homozygous mutant mice showed a lack of amidolytic activity.