PERA/EiJ

Stock number: 000930
Research areas: Research Tools

Description

Both PERA and PERC (Stock No. 001307) were derived from wild mice trapped in Peru. Wild-derived mice are genetically distinct from common laboratory mice for a number of complex phenotypic characteristics and are valuable tools for genetic mapping, evolution and systematics research.

Detailed description

Both PERA and PERC (Stock No. 001307) were derived from wild mice trapped in Peru. PERA mice exhibit a moderate susceptibility to induced experimental autoimmune encephalitis (EAE). In comparison to other strains, disease onset is late, disease severity is high, and the mortality rate is 60% with a 50% spontaneous relapse. Wild-derived mice are genetically distinct from common laboratory mice for a number of complex phenotypic characteristics and are valuable tools for genetic mapping, evolution and systematics research.

Development

In 1961, founders were trapped for ME Wallace, University of Cambridge, by O Atteck in a Peruvian Yard that was used to dry maize cobs in Nana Village, Rimac Valley, Peru. These mice were held in a small, closed colony by Wallace. In 1971, at approximately F25, members of this colony were sent to EM Eicher and TH Roderick at The Jackson Laboratory where inbreeding continued. In 2003 this inbred strain reached F88.

Allele

Symbol: Lith9^PERA/EiJ
Name: PERA/EiJ
MGI accession ID: MGI:2681423
Generation method: QTL
Marker symbol: Lith9
Marker name: lithogenic gene 9
Chromosome: 17
Strain of origin: PERA/EiJ
Molecular note: This allele confers increased gallstone score compared to I/LnJ. This allele confers susceptibility to gallstone formation compared to DBA/2J.
General note: Lith9 exhibits additive inheritance.

Allele

Symbol: Ahr^b-2
Name: b-2 variant
MGI accession ID: MGI:2667355
Generation method: Not Applicable
Marker symbol: Ahr
Marker name: aryl-hydrocarbon receptor
Chromosome: 12
Strain of origin: BALB/cBy
Molecular note: This allele encodes a high affinity, heat labile, 104 kDa receptor containing 848 amino acids. Sequencing studies of cDNA from C57BL/6J congenic mice homozygous for this allele identified nucleotide substitutions in the ORF that would cause 5 amino acid differences between the C57BL/6J and BALB/cBy peptides, and 2 amino acid differences between the BALB/cBy and DBA/2J peptides. A T to C transition in exon 11 replaces the opal termination codon in the C57BL/6J allele with an arginine codon in the BALB/cBy allele. This change would extend translation of the BALB/cBy mRNA by 43 amino acids, accounting for the larger size of the peptide produced by this allele (104 kDa, vs 95 kDa for the C57BL/6J allele).
General note: C57BL/6 carries the responsive Ahr^b allele; DBA/2 carries nonresponsive Ahr^d. Heterozygotes (Ahr^b/Ahr^d) are responsive (J:5282). Later work identified a second (J:8895) and later a third (J:22144) allele conferring response. Thus the allele in C57, C58, and MA/My strains is now Ahr^b-1; Ahr^b-2 is carried by BALB/cBy, A, and C3H; and Ahr^b-3 by Mus spretus, M. caroli, and MOLF/Ei. The nonresponsive strains AKR, DBA/2, and 129 carry Ahrd (J:22144). Nucleotide and amino acid sequence differences between Ahr^b-1 and Ahr^d have been determined (J:17460).

Strain of origin - this allele was found in BALB/cByJ, A/J, C3H/HeJ, CBA strains

Allele

Symbol: Mx1^s2
Name: myxovirus susceptibility 2
MGI accession ID: MGI:3715155
Generation method: Spontaneous
Attributes: Null/Knockout
Marker symbol: Mx1
Marker name: MX dynamin-like GTPase 1
Chromosome: 16
Strain of origin: multiple strains
Molecular note: CBA/J, CE/J, I/LnJ and PERA/Ei strains have a nonsense mutation that results in a null allele and susceptibility to myxoviruses.
General note:

The Mx genes determine resistance to the lethal effects of various myxoviruses including neurotropic avian influenza A virus injected intracerebrally, pneumotropic strains injected intranasally, and a hepatotropic strain injected intraperitoneally (J:5645, J:13136). Resistance is not dependent on presence of the thymus and is not abolished by immunosuppression or by inhibitors of macrophage function (J:5735, J:5478, J:5645). Resistance is specific for the orthomyxoviruses (J:6265). It is dependent on the presence of interferon-alpha and -beta but not -gamma (J:7365).

The resistance allele at the Mx1 locus, under induction by alpha/beta interferon, produces the 75 kDa protein MX-1, which confers resistance to the influenza virus, in the nuclei of cells carrying the allele. Susceptibility alleles do not produce the protein (J:8273). The protein is located in the nucleus (J:7703) and produces its antiviral effect by preventing synthesis of viral mRNA in the nucleus (J:7992). Nuclear localization is necessary for anti-influenza virus activity (J:1417), but mutations induced in Mx1 showed that nuclear position was not sufficient for the effect; mutations in several domains can cause its loss (J:11840). The MX-1 protein is a GTPase containing a GTP binding domain (J:1417) and this binding core is also necessary (J:21243).

Resistance is expressed by macrophages and other cells in vitro (J:6649, J:5940) but could not be transferred to susceptible animals by transfer of macrophages from resistant mice (J:6149).

Resistance to infection with two tick-borne viruses, Thogoto virus (J:8273) and Dhori virus (J:27760), is also conferred by Mx1^r.

The Mx1^r allele occurs only in strains A2G, SL/NiA, and T9, the latter being a strain derived from an influenza-resistant wild stock, and CAST/Ei, derived from Mus musculus castaneus. Most inbred strains, including C57BL/6J, C3H/HeJ, and BALB/cJ, carry an influenza susceptible Mx1^s1 allele which produces mRNA lacking exons 9, 10, and 11 of the Mx1^r allele. This large deletion apparently renders the protein incapable of providing resistance to influenza. The CBA/J, CE/J, I/LnJ, and PERA/Ei strains, also susceptible to the virus, have another form of the Mx1^s2 allele in which there is a nonsense mutation (J:9452).

Interferon is induced by viral infection and in turn induces the Mx protein (J:7703). Although some interferon-induced genes respond directly to virus invasion as well as indirectly through induction by virus-induced interferon, this primary response is very weak for the MX-1 protein in response to either influenza or Newcastle disease viruses (J:1892).