BXSB.129S2(C)-Cd1^tm1Gru/DcrJ

Stock number: 021565
Product name: CD1^-
Strain synonyms: BXSB-Cd1-/-, CD1-deficient BXSB.Yaa, BXSB.Yaa Cd1d1/Cd1d2-/-, BXSB.Yaa CD1-/-
Research areas: Immunology, Inflammation and Autoimmunity Research, Internal/Organ Research, Mouse/Human Gene Homologs, Research Tools

Description

BXSB.Yaa CD1-/- (BXSB.Yaa Cd1d1/Cd1d2-/-) mice are a BXSB-congenic strain carrying a null mutation of the CD1 antigen complex that abolished both CD1.1 (Cd1d1) and CD1.2 (Cd1d2) expression; resulting in natural killer T cell (NKT)-deficiency. These BXSB.Yaa CD1-/- mice may be useful in studying the role of natural killer T cells (NKTs) in spontaneous lupus-like autoimmune syndrome.

Detailed description

BXSB.Yaa CD1-/- (BXSB.Yaa Cd1d1/Cd1d2-/-) mice are a BXSB-congenic strain carrying a null mutation of the CD1 antigen complex; both CD1.1 (Cd1d1) and CD1.2 (Cd1d2) expression is abolished. Homozygous (CD1-/-) mice are natural killer T cell (NKT)-deficient.

Homozygous mice are viable and fertile. Both homozygous and heterozygous mice develop spontaneous lupus-like autoimmune syndrome similarly to BXSB/MpJ inbred mice (Stock No. 000740): mortality in males starts at ~13 weeks of age with 50% lethality by ~30 weeks and 76% lethality by ~40 weeks. Females develop a greatly attenuated form of autoimmune disease because they lack Yaa.

BALB/c-congenic mice harboring this null mutation of the CD1 antigen complex are described and available from The Jackson Laboratory Repository as Stock No. 003814.

Development

The murine CD1 locus is composed of two closely linked genes, CD1.1 (Cd1d1) and CD1.2 (Cd1d2), arranged in opposite transcriptional orientations and separated by an ~9 kbp intergenic region. Dr. Michael J. Grusby (Harvard Medical School) created the CD1 null allele (Cd1^tm1Gru) with a single targeting event that (i) replaced most of the Cd1d1 locus with a neomycin selection cassette, (ii) deleted the Cd1d2 locus, and (iii) retained the intergenic region. BALB/c-congenic mice harboring this null mutation of the CD1 antigen complex are described and available from The Jackson Laboratory Repository as Stock No. 003814.


Dr. Derry C. Roopenian (The Jackson Laboratory) obtained some of these mutant mice and backcrossed them with BXSB/MpJ inbred mice (Stock No. 000740) for 12 generations, and then maintained the colony by breeding homozygous mice together. In 2002, Dr. Roopenian froze embryos from BXSB.Yaa CD1-/- mice at generation N12. In 2013, this frozen stock was transferred to The Jackson Laboratory Repository (Autoimmune Resource) to establish Stock No. 021565. Male mice have the BXSB/MpJ-derived Y chromosome that contains the Y-linked autoimmune accelerator locus (Yaa).

Allele

Symbol: Cd1^tm1Gru
Name: targeted mutation 1, Michael Grusby
MGI accession ID: MGI:1857482
Generation method: Targeted
Attributes: Null/Knockout
Synonyms: CD1^-; CD1d KO; Cd1d^-; Cd1d1/Cd1d2^tm1Gru; CD1tm1Gru
Marker symbol: Cd1
Marker name: CD1 antigen complex
Chromosome: 3
Strain of origin: 129S2/SvPas
Molecular note: Both the Cd1d1 gene and the adjacent Cd1d2 gene were mutated in this allele. The coding sequence of Cd1d1 was replaced with a neomycin selection cassette and the coding sequence of Cd1d2 was deleted; however, the intergenic sequence was retained. Flow cytometric analysis on thymocytes derived from homozygous mice confirmed that no stable encoded protein was expressed on the cell surface.

Allele

Symbol: Yaa
Name: accelerated autoimmunity and lymphoproliferation
MGI accession ID: MGI:1856277
Generation method: Spontaneous
Synonyms: Is(XOfd1-Mid1;Y)1Mp; Tp(X;Y)1Ekw
Marker symbol: Yaa
Marker name: accelerated autoimmunity and lymphoproliferation transposition
Marker synonyms: Tp(X;Y)1Ekw
Chromosome: Y
Strain of origin: SB/Le
Molecular note: An approximately 4 MB region of the X chromosome that includes at least 13 known genes (spanning from Ofd1 to Mid1) was translocated to the Y chromosome adjacent to the pseudoautosomal region. Increased RNA expression of Msl3, Tlr7, Tmsb4x and Rab9 was detected in follicular B cells.