NZM2410.129X1-Fcgrt^tm1Dcr/DcrJ

Stock number: 003989
Product name: FcRn^-
Research areas: Immunology, Inflammation and Autoimmunity Research, Research Tools

Description

These Fcgrt knock-out mice exhibit low plasma albumin concentrations and are resistant to several experimentally induced autoimmune disorders, and are sensitive to experimentally induced Lyme's disease arthritis.

Detailed description

The neonatal Fc receptor, which is encoded by Fcgrt bound non-covalently to beta-2 microglobulin, facilitates the uptake of IgG through intestinal epithelial cells, protects IgG and albumin from degradation, and is involved in clearance of amyloid beta peptide from the brain. Mice that are homozygous for Fcgrt^tm1Dcr, a knockout allele, are viable and fertile. No Fcgrt gene product (mRNA or protein) is detected by quantitative PCR analysis of liver cDNA or Western blot analysis of small intestine from homozygotes. Homozygotes exhibit plasma albumin concentrations approximately 45% of levels observed in wildtype controls, reduced IgG levels and diminished perinatal maternal IgG transport. Fcgrt^tm1Dcr homozygotes are resistant to experimentally induced, serum-transfer autoimmune arthritis, as well as experimentally induced bullous pemphigoid, pemphigus foliaceus, and pemphigus vulgaris. Homozygotes are more sensitive to experimentally induced Lyme's disease arthritis, with more severe ankle swelling, joint involvement and decreased serum levels of anti Borrelia burgdorferi antibodies. IgG is accumulated in the glomerular basement membranes of aging mutants, and clearance of IgG from the kidneys is impaired.

In an attempt to offer alleles on well-characterized or multiple genetic backgrounds, alleles are frequently moved to a genetic background different from that on which an allele was first characterized. This is the case for the strain above. It should be noted that the phenotype could vary from that originally described. We will modify the strain description if necessary as published results become available.

Development

The Fcgrt^tm1Dcr allele was backcrossed from B6.129X1-Fcgrt^tm1Dcr/DcrJ (Stock #003982) onto the NZM2410/J host background by repeated backcrossing to this inbred in the laboratory of Dr. Derry Roopenian. This congenic was sibling intercrossed to homozygosity and sperm were cryopreserved in 2007 from homozygous males at generation N11F21.

Allele

Symbol: Fcgrt^tm1Dcr
Name: targeted mutation 1, Derry C Roopenian
MGI accession ID: MGI:3511510
Generation method: Targeted
Attributes: Null/Knockout
Synonyms: FcRn^-
Marker symbol: Fcgrt
Marker name: Fc receptor, IgG, alpha chain transporter
Marker synonyms: alpha-chain; FcgammaRn; FCRN; neonatal Fc receptor
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.