In other species: dog

Categories: Immune system phene

Links to possible relevant human trait(s) and/or gene(s) in OMIM: 601457 (trait) , 179615 (gene) , 179616 (gene)

Links to relevant human diseases in MONDO:

• MONDO:0011086: severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-positive

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal recessive

Disease-related: yes

Key variant known: no

Key variant is published: no

Species-specific symbol: T-B-NK+ SCID

Species-specific description: This disorder was created via the TALEN technology (Lee et al., 2014). Genetically-modifed organism; GMO.

Molecular basis: Lee et al. (2014) artificially created SCID pigs via "a reporter-guided transcription activator-like effector nuclease (TALEN) system" which was used to knock out the RAG2 gene (mutations in which are known to be causal of SCID in humans) in porcine somatic cells, which were then used in somatic-cell nuclear transfer to create pigs homozygous for the inactivated RAG2 allele. Huang et al. (2014) used similar strategies to create causal mutations in RAG1 and RAG2: "Piglets with biallelic mutations in either RAG1 or RAG2 exhibited hypoplasia of immune organs, failed to perform V(D)J rearrangement, and lost mature B and T cells". Using somatic cell nuclear transfer and gene targeting, Ito et al. (2014) also created RAG1 mutant SCID pigs.

Genetic engineering: Yes - variants have been created artificially, e.g. by genetic engineering or gene editing
Have human generated variants been created, e.g. through genetic engineering and gene editing

Clinical features: As reported by Lee et al. (2014), "Biallelically modified pigs either lacked a thymus or had one that was underdeveloped. Their splenic white pulp lacked B and T cells. Under a conventional housing environment, the biallelic RAG2 mutants manifested a “failure to thrive” phenotype, with signs of inflamma-tion and apoptosis in the spleen compared with age-matched wild-type animals by the time they were 4 wk of age. Pigs raised in a clean environment were healthier and, following injection of hu-man induced pluripotent stem cells (iPSCs), quickly developed ma-ture teratomas representing all three germ layers. The pigs also tolerated grafts of allogeneic porcine trophoblast stem cells. These SCID pigs should have a variety of uses in transplantation biology".

Associated genes: