BXSB.129X1-Fcgrt^tm1Dcr/J

Stock number: 021455
Product name: FcRn^-
Research areas: Immunology, Inflammation and Autoimmunity Research, Mouse/Human Gene Homologs, Research Tools

Description

FCGRT-deficient BXSB.Yaa mice (BXSB.Yaa FCGRT-/- or BXSB.Yaa FcRn-/-) are a BXSB-congenic strain carrying an FcRn null mutation. These mice may be useful in studying the role of the FcRn pathway in spontaneous lupus-like autoimmune syndrome.

Detailed description

FCGRT-deficient BXSB.Yaa mice (BXSB.Yaa FCGRT-/- or BXSB.Yaa FcRn-/-) are a BXSB-congenic strain carrying an FcRn null mutation. Homozygous (FCGRT-/-) mice lack the Fc receptor (FcRn), which normally functions to enhance the presentation of immune-complexed antigens by MHC class II molecules and is critical for maintaining normal concentrations of immunoglobulin G (IgG) antibodies and serum albumin.

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. The donating investigator also reports that FcRn-/- mice exhibit ~50% reduction in IgG.

C57BL/6J-congenic mice harboring the FcRn null allele are described and available from The Jackson Laboratory Repository as Stock No. 003982.

Development

The FcRn null allele (Fcgrt^tm1Dcr) was designed by Dr. Derry C. Roopenian (The Jackson Laboratory) with a PGK-neomycin cassette replacing exons 1-2 of the Fcgrt gene (Fc receptor, IgG, alpha chain transporter) on chromosome 7. C57BL/6J-congenic mice harboring this FcRn null allele are described and available from The Jackson Laboratory Repository as Stock No. 003982.


Dr. Roopenian backcrossed mice harboring the FcRn null mutation with BXSB/MpJ inbred mice (Stock No. 000740) for 11 generations, and then maintained the colony by breeding homozygous mice together. In 2012, Dr. Roopenian froze sperm from BXSB.Yaa FCGRT-/- mice at generation N11F30. In 2013, this frozen sperm was transferred to The Jackson Laboratory Repository (Autoimmune Resource) to establish Stock No. 021455. Male mice have the BXSB/MpJ-derived Y chromosome that contains the Y-linked autoimmune accelerator locus (Yaa).

Allele

Symbol: Fcgrt^tm1Dcr
Name: targeted mutation 1, Derry C Roopenian
MGI accession ID: MGI:3511510
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Fcgrt
Marker name: Fc receptor, IgG, alpha chain transporter
Chromosome: 7
Strain of origin: 129X1/SvJ
Molecular note: Sequence from exon 1 and part of exon2 was replaced with a PGK-neo cassette. Quantitative PCR of liver cDNA indicated the absence of mRNA. Western blot analysis of neonatal intestinal extracts failed to reveal protein product.

Allele

Symbol: Yaa
Name: accelerated autoimmunity and lymphoproliferation
MGI accession ID: MGI:1856277
Generation method: Spontaneous
Marker symbol: Yaa
Marker name: accelerated autoimmunity and lymphoproliferation transposition
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.