scholarly journals T cell receptor gamma and delta gene junctional sequences in SCID mice: excessive P nucleotide insertion.

1991 ◽  
Vol 174 (4) ◽  
pp. 769-773 ◽  
Author(s):  
L J Kienker ◽  
W A Kuziel ◽  
P W Tucker
Keyword(s):  
T Cell ◽  
T Cell Receptor ◽  
Severe Combined Immunodeficiency ◽  
Cell Receptor ◽  
Scid Mice ◽  
Combined Immunodeficiency ◽  
Joint Formation ◽  
P Elements ◽  
Nucleotide Addition ◽  
Nucleotide Insertion

The severe combined immunodeficiency (SCID) mutation has been postulated to affect a V(D)J recombinase activity involved in coding joint formation. Analysis of 38 joints from 34 distinct sequences of normally rearranged T cell receptor (TCR) gamma and delta genes from adult, SCID thymocytes reveals coding joints with an increased number of P nucleotides. One-third of P sequences are greater than or equal to 4 nucleotides in length and P elements of up to 15 bases are observed. This suggests that the SCID defect deregulates P nucleotide addition. Consequently, essential V(D)J recombination intermediates may seldom be generated.

scholarly journals An expanded population of natural killer cells in mice with severe combined immunodeficiency (SCID) lack rearrangement and expression of T cell receptor genes.

1986 ◽  
Vol 164 (5) ◽  
pp. 1797-1802 ◽  
Author(s):  
R J Lauzon ◽  
K A Siminovitch ◽  
G M Fulop ◽  
R A Phillips ◽  
J C Roder
Keyword(s):  
T Cell ◽  
Nk Cells ◽  
T Cell Receptor ◽  
Cell Function ◽  
Nk Cell ◽  
Severe Combined Immunodeficiency ◽  
Cell Receptor ◽  
Scid Mice ◽  
Combined Immunodeficiency ◽  
T Cell Receptor Genes

Mice with severe combined immunodeficiency syndrome (SCID) exhibit an impairment in both T and B cell maturation, whereas myelopoiesis remains unaffected. We report here that spleens from SCID mice have undergone phenotypic expansion of cells bearing the NK-2 and asialo GM1 markers (70-80%) characteristic of NK cells and this expansion is accompanied by a 3-4-fold enrichment in NK cytolytic activity over their normal C.B-17 littermates. Furthermore, the NK cells from SCID mice do not rearrange or express T cell receptor alpha or beta genes, or a third T cell rearranging gene, gamma. These findings suggest that (a) T cell receptors are not necessary for NK-mediated cytolysis, and (b) either NK cells constitute an entirely distinct lineage or NK cell function is acquired in pre-T cells prior to the expression of T cell receptor genes.

Biased T-cell receptor delta element recombination in scid thymocytes

1993 ◽  
Vol 13 (6) ◽  
pp. 3632-3640
Author(s):  
A M Carroll ◽  
J K Slack ◽  
W T Chang
Keyword(s):  
T Cell ◽  
T Cell Receptor ◽  
Severe Combined Immunodeficiency ◽  
Cell Receptor ◽  
Lymphocyte Development ◽  
Gene Rearrangements ◽  
Combined Immunodeficiency ◽  
Full Understanding ◽  
Wild Type

Thymocytes in mutant mice with severe combined immunodeficiency (scid thymocytes) show ongoing recombination of some T-cell receptor delta gene elements, generating signal joints quantitatively and qualitatively indistinguishable from those in wild-type fetal thymocytes. Excised D delta 2-J delta 1 and D delta 1-D delta 2 rearrangements are detectable at levels equivalent to or greater than those in thymocytes from wild-type mice on fetal day 15. Signal junctional modification, shown here to occur frequently in wild-type adult but not newborn excised D delta 2-J delta 1 junctions, can occur normally in adult scid thymocytes. Excised D delta 1-D delta 2 scid junctions, similar to wild-type thymocytes, include pseudonormal coding junctions as well as signal junctions. Inversional D delta 1-D delta 2 rearrangements, generating conventional hybrid junctions, are also reproducibly detectable in scid thymus DNA. These hybrids, unlike those reported for artificial recombination constructs, do not show extensive nucleotide loss. In contrast to the normal or high incidences of D delta 1-, D delta 2-, and J delta 1-associated signal junctions in scid thymocytes, V delta 1, V gamma 3, and V gamma 1.2 signal products are undetectable in scid thymocytes or are detectable at levels at least 10-fold lower than the levels in wild-type fetal thymocytes. These findings confirm biased T-cell receptor element recombination by V(D)J recombinase activity of nontransformed scid thymocytes and indicate that analysis of in vivo-mediated gene rearrangements is important for full understanding of how the scid mutation arrests lymphocyte development.

scholarly journals Biased T-cell receptor delta element recombination in scid thymocytes.

1993 ◽  
Vol 13 (6) ◽  
pp. 3632-3640 ◽  
Author(s):  
A M Carroll ◽  
J K Slack ◽  
W T Chang
Keyword(s):  
T Cell ◽  
T Cell Receptor ◽  
Severe Combined Immunodeficiency ◽  
Cell Receptor ◽  
Lymphocyte Development ◽  
Gene Rearrangements ◽  
Combined Immunodeficiency ◽  
Full Understanding ◽  
Wild Type

Thymocytes in mutant mice with severe combined immunodeficiency (scid thymocytes) show ongoing recombination of some T-cell receptor delta gene elements, generating signal joints quantitatively and qualitatively indistinguishable from those in wild-type fetal thymocytes. Excised D delta 2-J delta 1 and D delta 1-D delta 2 rearrangements are detectable at levels equivalent to or greater than those in thymocytes from wild-type mice on fetal day 15. Signal junctional modification, shown here to occur frequently in wild-type adult but not newborn excised D delta 2-J delta 1 junctions, can occur normally in adult scid thymocytes. Excised D delta 1-D delta 2 scid junctions, similar to wild-type thymocytes, include pseudonormal coding junctions as well as signal junctions. Inversional D delta 1-D delta 2 rearrangements, generating conventional hybrid junctions, are also reproducibly detectable in scid thymus DNA. These hybrids, unlike those reported for artificial recombination constructs, do not show extensive nucleotide loss. In contrast to the normal or high incidences of D delta 1-, D delta 2-, and J delta 1-associated signal junctions in scid thymocytes, V delta 1, V gamma 3, and V gamma 1.2 signal products are undetectable in scid thymocytes or are detectable at levels at least 10-fold lower than the levels in wild-type fetal thymocytes. These findings confirm biased T-cell receptor element recombination by V(D)J recombinase activity of nontransformed scid thymocytes and indicate that analysis of in vivo-mediated gene rearrangements is important for full understanding of how the scid mutation arrests lymphocyte development.

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