B6N.DDD-plt/NknoJ

Stock number: 012866
Research areas: Cancer Research, Cardiovascular Research, Developmental Biology Research, Hematological Research, Immunology, Inflammation and Autoimmunity Research, Internal/Organ Research, Research Tools

Description

These C57BL/6-plt mice harbor the spontaneous plt (or "paucity of lymph node T cells") deletion of the Ccl19 and Ccl21a loci on chromosome 4. Lack of expression of these two CCR7 receptor ligands in the secondary lymphoid organs results in abnormal leukocyte migration and impaired immune response. These mutant mice may be useful in studying leukocyte migration into lymphatic tissues, elucidating differences between T cell and B cell trafficking, and the role of stromal cells in bringing naive T cells and dendritic cells together for the initiation of immune responses.

Detailed description

Homozygous C57BL/6-plt mice are viable and fertile, harboring the spontaneous plt (or "paucity of lymph node T cells") deletion of both the Ccl19 and Ccl21a loci on chromosome 4. Lack of expression of these two CCR7 ligands in the secondary lymphoid organs results in abnormal leukocyte migration and impaired immune response. Specifically, homozygous mice have disrupted trafficking/homing of T cells and dendritic cells to lymphoid tissues. No reported abnormalities in B cell distribution/cellularity are reported for homozygous mice. Transient migration of antigen-stimulated B cells in lymphoid organs (which facilitates B cell/helper T cell interactions) is also impaired in homozygous mice. Homozygous mice exhibit mature single-positive thymocyte arrest in the thymic cortex that results in defective formation of the medullary region of the thymus. Thymic export of T cells in these mice is compromised during the neonatal period but not in adulthood. While CCL21 expression is absent in lymphoid organs because of the Ccl21a deletion, CCL21 expression in non-lymphoid organs is observed because the upstream Cc121b locus remains intact. These C57BL/6-plt mice may be useful in studying leukocyte migration into lymphatic tissues, elucidating differences between T cell and B cell trafficking, and the role of stromal cells in bringing naive T cells and dendritic cells together for the initiation of immune responses.

The donating investigator provided these C57BL/6-plt mice, as well as plt mice congenic on a BALB/c genetic background (BALB/c-plt ; Stock No. 012873). The donating investigator reports dendritic cell migration is severely impaired in both homozygous strains. In addition, they report T cell homing to lymph nodes is severely impaired in BALB/c-plt homozygotes, but mildly impaired in C57BL/6-plt homozygotes. BALB/c-plt homozygous mice have been shown to allow enhanced survival of MHC-mismatched islet allografts (this phenotype is not characterized for C57BL/6-plt mice)[July 2010]).

Development

In 1997, Dr. Hideki Nakano (while at the Laboratory Animal Research Center, University of Tokyo, Japan) reported that their colony of DDD/1 inbred mice exhibited greatly diminished T cell numbers in lymph nodes. This spontaneous deletion, designated plt (or "paucity of lymph node T cells"), behaves as a single autosomal recessive allele and deletes a portion of chromosome 4 including both the Ccl19 (Epstein-Barr virus-induced molecule-1 ligand chemokine [ELC], ELC-atg, or Scya19) and Ccl21a (6CKine-ser, 6CKBAC2, secondary lymphoid organ chemokine [SLC], SLC-Ser) loci. Some plt-mutant mice were backcrossed to C57BL/6NCrl for eleven generations to generate the C57BL6-plt congenic strain. Dr. Hideki Nakano (while at NIEHS/NIH, Research Triangle Park. North Carolina USA) sent homozygous C57BL6-plt females and males to The Jackson Laboratory Repository in 2010. Upon arrival, C57BL6-plt mice were bred together to maintain the colony. During backcrossing, the Y chromosome may not have been fixed to the C57BL/6NCrl genetic background.

The donating investigator reports that C57BL6-plt mice should have retained the plt haplotype at the Chemokine Locus on Mouse Chromosome 4 (Cklc4^plt). Thus the genomic organization of Cklc4 would be the same as DDD/1-plt mice: Ccl21b intact and functional (Ccl21a deleted), Scya19-ps1 (Ccl19-ps1) intact (Scya19 [Ccl19] deleted), Scya27a (Ccl27a) intact and functional, and Il11ra1 intact and functional. The Jackson Laboratory will verify these mice harbor the plt deletion, but will not extensively verify the genetic composition of the other loci described for the Cklc4^plt haplotype. The Cklc4^plt haplotype will need to be verified by the investigator using the mice if necessary.

Allele

Symbol: plt
Name: paucity of lymph node T-cells
MGI accession ID: MGI:1857881
Generation method: Spontaneous
Marker symbol: plt
Marker name: paucity of lymph node T cells
Chromosome: 4
Strain of origin: DDD/1
Molecular note: This mutation is a deletion region on chromosome 4 which includes the Ccl19 and Ccl21a genes (see also revised nomenclature for the Ccl21 family of genes).