This allele confers susceptibility to flavivirus infection. Susceptible mouse strains produce a protein lacking 30% of the C-terminal region due a nucleotide substitution. The C820T transition results in a premature stop codon.
This revertant to wild-type of the Tlr4Lps-d, defective lipopolysaccharide response, allele was identified in a screen for LPS responsiveness of several C3H/He sublines maintained at Australian facilities. Sequence analysis of Tlr4 in the vicinity of the original mutation, which replaced C with A at nucleotide position 2342 and changed a triplet (CCT) encoding proline with a codon (CAT) for histidine in the third exon, demonstrated that C3H/HeJArc and its derivative congenic strains bear a Tlr4 allele identical in sequence to wild-type. As Tlr4Lps-d occurred in C3H/HeJ between 1958 and 1965 (J:5919) and C3H/HeJArc has been maintained at the Animal Resources Centre in Murdoch, WA, Australia since no earlier than 1971 (J:169915), the apparent wild-type allele in this strain is presumed to have arisen by reverse mutation.
Flv phenotype:- Susceptible to infections by Flaviviruses.
Tlr4 Phenotype:- responsiveness of Toll 4 Receptor to LPS infection.
Diht Phenotype:- a decreased hypothermia response as measured by drop in core temperature following the peripheral administration of a dopamine agonist
Phenotype Heterozygous State
Flvs Phenotype:- recessive phenotype, hets are resistant to infection by Flaviviruses.
Tlr4 phenotype:- is dominant and heterozygous mice show responsiveness to LPS.
Dihtlow phenotype is recessive and dopamine-induced hypothermia in heterozygotes show the high responder type.
Hypothermia phenotype was performed by taking rectal temperatures following peripheral administration of a dopamine agonist. Protocol can be found in Stoddart et al 2004. Flavivirus susceptibility was measured as mortality and brain virus titres following IC inoculation with a Flavivirus (MVE). See Urosevic et al 1997. Assessment of LPS responsiveness described in Silvia and Urosvic 1999.
Fertility and Strain maintenance
Fertility and Strain maintenance
Are homozygous mice viable?
Are homozygous mice fertile?
Are heterozygotes / hemizygotes* fertile?
* Hemizygote as used here refers to males carring a mutation on the X chromosome or mice of either sex
carrying an inserted transgene with no homologous allele on the other chromosome.
brother x sister
Homozygous Matings Required?
This strain was originally derived from C3H/HeJ mice from the Jackson laboratory. The strain has been maintained in Western Australia for over 30 years and has since been identified to show some genetic drift. In particular, a point mutation in the Tlr4 receptor gene on Chr4 has lead to the recovery of lipopolysaccharide (LPS) responsiveness of the Toll4 receptor protein in C3H/HeJARC. C3H/HeJ mice from the original Jackson colony are unresponsive to LPS. The C3H/HeJARC mice also form the genetic backgrond for other congenic C3H/ mouse models of Flavivirus infecion and dopamine-induced hypothermia.
This strain forms part of a comparative congenic model used to investigate flavivirus susceptibility/resistance and dopamine related phenotypes. This strain shows susceptibility to flavivirus infection and is the genetic background control strain for congenic C3H strains resistant to flaviviruses. The hypothermia model has been developed using dopamine-induced hypothermia as the phenotypic marker and C3H/HeJARC responses show reduced dopamine-induced hyopthermia compared to mice possessing the Dihthigh allele.
Applicable Research Areas
Is the strain available in any form to other researchers