PMID- 20872248
OWN - NLM
STAT- MEDLINE
DCOM- 20110926
LR  - 20211020
IS  - 1573-9368 (Electronic)
IS  - 0962-8819 (Print)
IS  - 0962-8819 (Linking)
VI  - 20
IP  - 3
DP  - 2011 Jun
TI  - Generation of antibody- and B cell-deficient pigs by targeted disruption of the 
      J-region gene segment of the heavy chain locus.
PG  - 625-41
LID - 10.1007/s11248-010-9444-z [doi]
AB  - A poly(A)-trap gene targeting strategy was used to disrupt the single functional 
      heavy chain (HC) joining region (J(H)) of swine in primary fibroblasts. 
      Genetically modified piglets were then generated via somatic cell nuclear 
      transfer (SCNT) and bred to yield litters comprising J(H) wild-type littermate 
      (+/+), J(H) heterozygous knockout (+/-) and J(H) homozygous knockout (-/-) piglets 
      in the expected Mendelian ratio of 1:2:1. There are only two other targeted loci 
      previously published in swine, and this is the first successful poly(A)-trap 
      strategy ever published in a livestock species. In either blood or secondary 
      lymphoid tissues, flow cytometry, RT-PCR and ELISA detected no circulating IgM(+) 
      B cells, and no transcription or secretion of immunoglobulin (Ig) isotypes, 
      respectively in J(H) -/- pigs. Histochemical and immunohistochemical (IHC) 
      studies failed to detect lymph node (LN) follicles or CD79alpha(+) B cells, 
      respectively in J(H) -/- pigs. T cell receptor (TCR)(beta) transcription and T cells 
      were detected in J(H) -/- pigs. When reared conventionally, J(H) -/- pigs 
      succumbed to bacterial infections after weaning. These antibody (Ab)- and B 
      cell-deficient pigs have significant value as models for both veterinary and 
      human research to discriminate cellular and humoral protective immunity to 
      infectious agents. Thus, these pigs may aid in vaccine development for infectious 
      agents such as the pandemic porcine reproductive and respiratory syndrome virus 
      (PRRSV) and H1N1 swine flu. These pigs are also a first significant step towards 
      generating a pig that expresses fully human, antigen-specific polyclonal Ab to 
      target numerous incurable infectious diseases with high unmet clinical need.
FAU - Mendicino, M
AU  - Mendicino M
AD  - Revivicor, Inc., 1700 Kraft Drive, Blacksburg, VA 24060, USA.
FAU - Ramsoondar, J
AU  - Ramsoondar J
FAU - Phelps, C
AU  - Phelps C
FAU - Vaught, T
AU  - Vaught T
FAU - Ball, S
AU  - Ball S
FAU - LeRoith, T
AU  - LeRoith T
FAU - Monahan, J
AU  - Monahan J
FAU - Chen, S
AU  - Chen S
FAU - Dandro, A
AU  - Dandro A
FAU - Boone, J
AU  - Boone J
FAU - Jobst, P
AU  - Jobst P
FAU - Vance, A
AU  - Vance A
FAU - Wertz, N
AU  - Wertz N
FAU - Bergman, Z
AU  - Bergman Z
FAU - Sun, X-Z
AU  - Sun XZ
FAU - Polejaeva, I
AU  - Polejaeva I
FAU - Butler, J
AU  - Butler J
FAU - Dai, Y
AU  - Dai Y
FAU - Ayares, D
AU  - Ayares D
FAU - Wells, K
AU  - Wells K
LA  - eng
PT  - Evaluation Study
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20100926
PL  - Netherlands
TA  - Transgenic Res
JT  - Transgenic research
JID - 9209120
RN  - 0 (Antibodies)
RN  - 0 (Immunoglobulin Heavy Chains)
RN  - 0 (Immunoglobulin Isotypes)
RN  - 24937-83-5 (Poly A)
SB  - IM
MH  - Animals
MH  - Animals, Newborn
MH  - Antibodies/genetics/immunology/*metabolism
MH  - B-Lymphocytes/immunology/*metabolism
MH  - Bacterial Infections/immunology
MH  - Cells, Cultured
MH  - *Disease Models, Animal
MH  - Fibroblasts
MH  - *Gene Targeting
MH  - Genetic Engineering/methods
MH  - Humans
MH  - Immunoglobulin Heavy Chains/*genetics/metabolism
MH  - Immunoglobulin Isotypes/*genetics/metabolism
MH  - Immunohistochemistry
MH  - Poly A/*genetics
MH  - Swine
MH  - T-Lymphocytes/immunology/metabolism
MH  - Transfection
PMC - PMC7089184
COIS- M. Mendicino, J. Ramsoondar, C. Phelps, T. Vaught, S. Ball, Y. Dai, J. Monahan, 
      S. Chen, A. Dandro, J. Boone, P. Jobst, A. Vance, I. Polejaeva, K. Wells, and D. 
      Ayares are or were employees of Revivicor, Inc.
EDAT- 2010/09/28 06:00
MHDA- 2011/09/29 06:00
PMCR- 2020/03/23
CRDT- 2010/09/28 06:00
PHST- 2010/06/16 00:00 [received]
PHST- 2010/09/13 00:00 [accepted]
PHST- 2010/09/28 06:00 [entrez]
PHST- 2010/09/28 06:00 [pubmed]
PHST- 2011/09/29 06:00 [medline]
PHST- 2020/03/23 00:00 [pmc-release]
AID - 9444 [pii]
AID - 10.1007/s11248-010-9444-z [doi]
PST - ppublish
SO  - Transgenic Res. 2011 Jun;20(3):625-41. doi: 10.1007/s11248-010-9444-z. Epub 2010 
      Sep 26.