C.C3-Tlr4^Lps-d/J

Stock number: 002930
Research areas: Immunology, Inflammation and Autoimmunity Research

Description

In addition to the Tlr4^Lps-d congenic interval from C3H/HeJ, this strain is also congenic for the wild type tyrosinase allele from C3H/HeJ on chromosome 7. This strain provides a tool for analysis of markers in the region and for examining functional effects of Lps^d on BALB/c, a strain susceptible to infection, neoplastic disease including the induction of plasmacytomas and other tumors.

Detailed description

In addition to the Tlr4^Lps-d congenic interval from C3H/HeJ, this strain is also congenic for the wild type tyrosinase allele from C3H/HeJ on chromosome 7. This strain provides a tool for analysis of markers in the region and for examining functional effects of Lps^d on BALB/c, a strain susceptible to infection, neoplastic disease including the induction of plasmacytomas and other tumors.

Development

The Lps-d mutation arose in C3H/HeJ sometime between 1960 and 1968. In 1977 a C3H/HeJ female, derived from the colony of David Sachs at NIH, was crossed with a BALB/cAnPt male and the Tlr4^Lps-d allele was transferred onto the BALB/cAnPt background by continued backcrossing. At that time it was thought that Tlr4 and Tyrp1 were tightly linked so the agouti mice, those that would be carrying the C3H/HeJ-derived dominant B (wild-type) allele of Typr1 rather than being homozygous for the BALB/cAnPt-derived recessive b allele and Tyr^c allele, were selected at each generation to continue the backcross. At N6 intercrossing made the strain homozygous for Tlr4^Lps-d and Tyrp1^B. Backcrossing to BALB/cAnPt was resumed from N6F22. When backcrossing reached N20, the strain was intercrossed to generate this strain homozygous for Tlr4^Lps-d and Tyrp1^B but not Tyr^c. The congenic interval encompassing Tyrp1^B and Tlr4^Lps-d includes at least from D4Mit151 through D4Mit26. This strain was imported into The Jackson Laboratory from Dr.Stefanie Vogel at Uniformed Services University of the Health Sciences in 1997.

Allele

Symbol: Tlr4^Lps-d
Name: defective lipopolysaccharide response
MGI accession ID: MGI:1857718
Generation method: Spontaneous
Marker symbol: Tlr4
Marker name: toll-like receptor 4
Chromosome: 4
Strain of origin: C3H/HeJ
Molecular note: This allele corresponds to a mutation in the third exon of the gene. A C-to-A substitution at coding tide position 2135 (c.2135C>A) results in an amino acid substitution that replaces proline with histidine at position 712 (p.P712H).
General note: C3H/HeJ mice carry this allele. Various combinations of Lps-associated traits have been followed in crosses between C3H/HeJ and other C3H substrains, and the traits have in all cases segregated together (J:30692, J:5557, J:5593, J:5938). Some of the traits show dominance of the Tlr4^lps-n allele; others, including Tlr4^Lps-d, show codominance.

Genbank ID for this allele: AF095353