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Spontaneous Allele Detail
Symbol: Mx1s1
Name: MX dynamin-like GTPase 1; myxovirus susceptibility 1
MGI ID: MGI:3715154
Gene: Mx1  Location: Chr16:97248235-97264106 bp, - strand  Genetic Position: Chr16, 57.46 cM, cytoband C4
Alliance: Mx1s1 page
Strain of Origin:  multiple strains
Allele Type:    Spontaneous (Null/knockout)
Mutation:    Intragenic deletion
Mutation detailsMany inbred mouse strains have an exon 9 to 11 deletion, resulting in a null allele and susceptibility to myxoviruses, including: A/J, ABP/Le, AKR/J, AU/SsJ, BALB/cJ, BDP/J, BUB/BnJ, C3H/HeJ, C57BL/6J, C57BL/10J, C57BL/KsJ, C57L/J, C58/J, DA/HuSn, DBA/2J, FSB/GnEi, FVB/NJ, LIS/A, LP/J, MA/MyJ, MAS/A, NZB/BINJ, P/J, PL/J, RIIIS/J, RF/J, SEA/GnJ, SEC1/ReJ, SJL/J, ST/bJ, TS1/A, TW1/A. YBR/Ei, 020/A, 129/J, SF/CamEi and SK/CamEi. (J:9452, J:152634)
Inheritance:    Recessive
View phenotypes and curated references for all genotypes (concatenated display).
Find Mice (IMSR)
Mouse strains and cell lines available from the International Mouse Strain Resource (IMSR)
Carrying this Mutation:  Mouse Strains: 26 strains available      Cell Lines: 0 lines available
Carrying any Mx1 Mutation:  80 strains or lines available

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 Mx1r.

The Mx1r 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 Mx1s1 allele which produces mRNA lacking exons 9, 10, and 11 of the Mx1r 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 Mx1s2 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).

Original:  J:13136 LINDENMANN J, INHERITANCE OF RESISTANCE TO INFLUENZA VIRUS IN MICE. Proc Soc Exp Biol Med. 1964 Jun;116:506-9
All:  19 reference(s)

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