These mice harbor a "knockout" mutation of the Sepp1 (selenoprotein P, plasma, 1) gene and may be useful for studying selenium transport/metabolism/deficiency in neurology (progressive neurological dysfunction), reproductive biology (sperm development), and immunology (such as type 2 cytokine-associated myeloid cells, IL-10-dependent inflammatory responses, cirrhosis, and Crohn's disease).
Raymond F. Burk, Vanderbilt University
Mice heterozygous for this targeted mutation are viable and fertile. No RNA or selenoprotein P (Se-P) protein expression from the targeted gene is observed in plasma. Homozygous (Sepp1-deficient) mice are viable with altered selenium metabolism rendering them intolerant of low dietary selenium intake and resulting in significantly shortened life span. Homozygotes have lower brain selenium concentrations and develop progressive neurological dysfunction (impaired movement and coordination); the progression of which is preventable (but not reversible) with dietary selenium supplement. Homozygous females are fertile but have difficulty producing and raising pups. Homozygous males have sharply reduced fertility due to flagellar structural defects ("kinked sperm") which, unlike the neurological phenotype, are not prevented with dietary selenium supplement. Sepp1-deficient mice, supplemented with dietary selenium and infected with an African Trypanosomiasis parasite, exhibit increased tissue injury associated with increased production of reactive oxygen species and increased apoptosis in the liver immune cells, reduced parasite clearance capacity of myeloid cells, and decreased survival. These mutant mice may be useful for studying selenium transport/metabolism/deficiency in neurology (progressive neurological dysfunction), reproductive biology (sperm development), and immunology (such as type 2 cytokine-associated myeloid cells, IL-10-dependent inflammatory responses, cirrhosis, and Crohn's disease).
A targeting vector was designed to insert a Neo cassette (containing loxP sites) just downstream of the initiating ATG site in exon 2 of the targeted gene. The loxP sites within the Neo cassette result in translational stops in all three reading frames. The construct was electroporated into 129SV-derived embryonic stem (ES) cells. Correctly targeted ES cells were injected into recipient blastocysts and the resulting chimeric males were bred with C57BL/6J females. Next, mutant mice were backcrossed to C57BL/6J for at least 10 generations prior to arrival at The Jackson Laboratory. Upon arrival, mice were bred with C57BL/6J inbred mice (Stock No. 000664) to establish the colony.
|Allele Name||targeted mutation 1, Raymond F Burk|
|Allele Type||Targeted (Null/Knockout)|
|Gene Symbol and Name||Selenop, selenoprotein P|
|Strain of Origin||129|
|Molecular Note||The gene was disrupted by insertion of a neomycin resistance cassette into exon 2 via homologous recombination. The neo cassette carries stop codons in all 3 reading frames. Protein product was undetectable by Western blot and radioimmunoassay of plasma samples from homozygous mutant animals.|
|Mutations Made By|| |
Raymond Burk, Vanderbilt University
When maintaining a live colony, heterozygous mice may be bred. Homozygous males have sharply reduced fertility (sperm defect) and homozygous females have difficulty producing and raising pups (presumably due to neurological phenotype). Addition of selenium to the diet prevents progression of neurological dysfunction and may allow homozygous females to be used for breeding. Dietary selenium supplement does not prevent the homozygous male sperm defect.
When using the B6.129-Selenoptm1Rfb/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #008201 in your Materials and Methods section.