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.
Dr. Derry Roopenian, The Jackson Laboratory
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 Fcgrttm1Dcr, 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. Fcgrttm1Dcr 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.
The Fcgrttm1Dcr allele was backcrossed from B6.129X1-Fcgrttm1Dcr/DcrJ (Stock #003982) onto the MRL/MpJ 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 N11F22.
|Allele Name||targeted mutation 1, Derry C Roopenian|
|Allele Type||Targeted (Null/Knockout)|
|Gene Symbol and Name||Fcgrt, Fc receptor, IgG, alpha chain transporter|
|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.|
"MICE" means mouse strains, their progeny derived by inbreeding or crossbreeding, unmodified derivatives from mouse strains or their progeny supplied by The Jackson Laboratory ("JACKSON"). "PRODUCT(S)" means biological materials supplied by JACKSON, and their derivatives. "SERVICES" means projects conducted by JACKSON for other parties that may include but are not limited to the use of MICE or PRODUCTS. "RECIPIENT" means each recipient of MICE, PRODUCTS, or SERVICES provided by JACKSON including each institution, its employees and other researchers under its control. MICE or PRODUCTS shall not be: (i) used for any purpose other than internal research, (ii) sold or otherwise provided to any third party for any use, or (iii) provided to any agent or other third party to provide breeding or other services. Acceptance of MICE, PRODUCTS or SERVICES from JACKSON shall be deemed as agreement by RECIPIENT to these conditions, and departure from these conditions requires JACKSON’s prior written authorization.
MICE, PRODUCTS AND SERVICES ARE PROVIDED "AS IS". JACKSON EXTENDS NO WARRANTIES OF ANY KIND, EITHER EXPRESS, IMPLIED, OR STATUTORY, WITH RESPECT TO MICE, PRODUCTS OR SERVICES, INCLUDING ANY IMPLIED WARRANTY OF MERCHANTABILITY OR FITNESS FOR A PARTICULAR PURPOSE, OR ANY WARRANTY OF NON-INFRINGEMENT OF ANY PATENT, TRADEMARK, OR OTHER INTELLECTUAL PROPERTY RIGHTS.
In case of dissatisfaction for a valid reason and claimed in writing by a purchaser within ninety (90) days of receipt of, PRODUCTS or SERVICES, JACKSON will, at its option, provide credit or replacement for the PRODUCT received or the SERVICES provided; JACKSON makes no other representations and this shall be the exclusive remedy of the purchaser. Please note specific policy for live mice.
Consistent with the requirement for a written understanding regarding animal care and use, the JACKSON Animal Care and Use Committee will review the animal care and use protocol(s) associated with any SERVICES to be performed at JACKSON, and JACKSON shall have ultimate responsibility and authority for the care of animals while on site or in JACKSON custody.
In no event shall JACKSON, its trustees, directors, officers, employees, and affiliates be liable for any causes of action or damages, including any direct, indirect, special, or consequential damages, arising out of the provision of MICE, PRODUCTS, or SERVICES, including economic damage or injury to property and lost profits, and including any damage arising from acts or negligence on the part of JACKSON, its agents or employees. Unless prohibited by law, in purchasing or receiving MICE, PRODUCTS, or SERVICES from JACKSON, purchaser or recipient, or any party claiming by or through them, expressly releases and discharges JACKSON from all such causes of action or damages, and further agrees to defend and indemnify JACKSON from any costs or damages arising out of any third party claims.
MICE, PRODUCTS or SERVICES are to be used in a safe manner and in accordance with all applicable governmental rules and regulations.
The foregoing represents the General Terms and Conditions applicable to JACKSON’s MICE, PRODUCTS or SERVICES. In addition, special terms and conditions of sale of certain MICE, PRODUCTS, or SERVICES may be set forth separately in JACKSON web pages, catalogs, price lists, contracts, and/or other documents, and these special terms and conditions shall also govern the sale of these MICE, PRODUCTS and SERVICES by JACKSON, and by its licensees and distributors.
Acceptance of delivery of MICE, PRODUCTS or SERVICES shall be deemed agreement to these terms and conditions. No purchase order or other document transmitted by purchaser or recipient that may modify the terms and conditions hereof, shall be in any way binding on JACKSON, and instead the terms and conditions set forth herein, including any special terms and conditions set forth separately, shall govern the sale of MICE, PRODUCTS or SERVICES by JACKSON.