OMIA 001574-9823 : Severe combined immunodeficiency disease, autosomal, T cell-negative, B cell-negative, NK cell-positive in Sus scrofa

In other species: dog

Possibly relevant human trait(s) and/or gene(s) (MIM number): 601457

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal Recessive

Considered a defect: 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.

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:

Symbol Description Species Chr Location OMIA gene details page Other Links
RAG1 recombination activating gene 1 Sus scrofa 2 NC_010444.4 (24573853..24565447) RAG1 Homologene, Ensembl, NCBI gene
RAG2 recombination activating gene 2 Sus scrofa 2 NC_010444.4 (24547605..24553944) RAG2 Homologene, Ensembl, NCBI gene

References


Note: the references are listed in reverse chronological order (from the most recent year to the earliest year), and alphabetically by first author within a year.
2014 Huang, J., Guo, X., Fan, N., Song, J., Zhao, B., Ouyang, Z., Liu, Z., Zhao, Y., Yan, Q., Yi, X., Schambach, A., Frampton, J., Esteban, M.A., Yang, D., Yang, H., Lai, L. :
RAG1/2 knockout pigs with severe combined immunodeficiency. J Immunol 193:1496-503, 2014. Pubmed reference: 24973446. DOI: 10.4049/jimmunol.1400915.
Ito, T., Sendai, Y., Yamazaki, S., Seki-Soma, M., Hirose, K., Watanabe, M., Fukawa, K., Nakauchi, H. :
Generation of recombination activating gene-1-deficient neonatal piglets: a model of T and B cell deficient severe combined immune deficiency. PLoS One 9:e113833, 2014. Pubmed reference: 25437445. DOI: 10.1371/journal.pone.0113833.
Lee, K., Kwon, D.N., Ezashi, T., Choi, Y.J., Park, C., Ericsson, A.C., Brown, A.N., Samuel, M.S., Park, K.W., Walters, E.M., Kim, D.Y., Kim, J.H., Franklin, C.L., Murphy, C.N., Roberts, R.M., Prather, R.S., Kim, J.H. :
Engraftment of human iPS cells and allogeneic porcine cells into pigs with inactivated RAG2 and accompanying severe combined immunodeficiency. Proc Natl Acad Sci U S A :, 2014. Pubmed reference: 24799706. DOI: 10.1073/pnas.1406376111.

Edit History


  • Created by Frank Nicholas on 14 May 2014
  • Changed by Frank Nicholas on 14 May 2014
  • Changed by Frank Nicholas on 31 Mar 2016
  • Changed by Frank Nicholas on 29 Sep 2016