BUB/BnJ

Stock number: 000653
Research areas: Hematological Research, Immunology, Inflammation and Autoimmunity Research, Mouse/Human Gene Homologs, Neurobiology Research, Research Tools, Sensorineural Research

Description

BUB/BnJ mice carry a specific T cell receptor V beta mutation, making this strain highly susceptible to collagen-induced arthritis. Mice are also reported to have high serum complement activity. BUB/BnJ mice are homozygous for the Mass1^frings allele (monogenic, audiogenic seizure susceptibility 1) and are susceptible to audiogenic seizures prior to 25 days of age. They also have early onset hearing impairment by 3-4 weeks of age.

Detailed description

BUB/BnJ mice carry a specific T cell receptor V beta mutation, making this strain highly susceptible to collagen-induced arthritis. This T cell receptor V beta restriction works in concert with other uncharacterized modifying genes present in BUB/BnJ mice. BUB/BnJ mice carry no detectable endogenous ecotropic MuLV DNA sequences. Mice are also reported to have high serum complement activity. In response to challenge, BUB/BnJ mice develop immune-mediated nephritis characterized by proteinuria, glomerulonephritis and tubulointerstitial disease (Xie et al., 2004).

BUB/BnJ mice are homozygous for the Adgrv1^frings allele (monogenic, audiogenic seizure susceptibility 1) and are susceptible to audiogenic seizures prior to 25 days of age (Skradski, et al 2001). In addition, the Adgrv1^frings allele acounts for early onset hearing impairment by 3-4 weeks of age (Johnson KR, et al 2005).

Development

The BUB/BnJ inbred strain originated from randomly bred albino mice of unknown ancestry. Inbreeding was begun in 1945 by JW Wilson at Brown University. This strain was transferred to S Bernstein at The Jackson Laboratory at F46 and then to the production facility in 1968 at generation F68. Current generation of inbreeding is F166+.

Allele

Symbol: Il3ra^m1
Name: mutation 1
MGI accession ID: MGI:3652833
Generation method: Spontaneous
Marker symbol: Il3ra
Marker name: interleukin 3 receptor, alpha chain
Chromosome: 14
Strain of origin: multiple strains
Molecular note: Sequence analysis revealed A/J mice lack the sequence corresponding to exon 8, which encodes 10 amino acid residues in the extracellular domain. Aberrant splicing was due to a 5 base pair deletion at the branch point in intron 7.
General note: This allele has been identified in A/J, A/WySnJ, A/HeJ, C58/J, RF/J, AKR/J, SM/J, BUB/BnJ, CE/J, and NZB/B1NJ. see J:24918.

Allele

Symbol: Cdh23^ahl
Name: age related hearing loss 1
MGI accession ID: MGI:3028349
Generation method: Spontaneous
Marker symbol: Cdh23
Marker name: cadherin 23 (otocadherin)
Chromosome: 10
Strain of origin: multiple strains
Molecular note: Genetic complementation tests have shown allelism between the mdfw (modifier of deaf waddler) locus and the ahl locus. Further analysis has shown this is caused by a G to A transition at coding nucleotide position 753 of Cdh23 (SNP rs257098870). This hypomorphic allele changes splice donor site G-GT to A-GT, causing frame skipping of exon 7. This is predicted to delete part of the 2nd and 3rd ectodomains and cause reduced message stability. Twenty-seven strains classified with ahl and carrying the 753A allele include: CD-1, RBF/DnJ, PL/J, AKR/J, RF/J, BALB/cBy, A/WySnJ, P/J, SENCARA/PtJ, DBA/1J, ALS/LtJ, C58/J, C57BLKS/J, 129P1/ReJ, C57BR/cd, SKH2/J, BUB/Bn, MA/MyJ, LP/J, 129X1/SvJ, NOR/LtJ, A/J, C57BL/6, NOD/LtJ, DBA/2J, ALR/LtJ, C57L/J. Strains classified with ahl that DO NOT carry this mutation include: 129S1/SvImJ, C3H/HeSnJ, I/LnJ, YBR/Ei, MRL/MpJ.

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: Pde6b^rd1
Name: retinal degeneration 1
MGI accession ID: MGI:1856373
Generation method: Spontaneous
Marker symbol: Pde6b
Marker name: phosphodiesterase 6B, cGMP, rod receptor, beta polypeptide
Chromosome: 5
Strain of origin: various
Molecular note: Two mutations have been identified in rd1 mice. A murine leukimia virus (Xmv-28) insertion in reverse orientation in intron 1 is found in all mouse strains with the rd1 phenotype. Further, a nonsense mutation (C-to-A transversion) in codon 347 that results in a truncation eliminating more than half of the predicted encoded protein, including the catalytic domain, has been identified in all rd1 strains of mice. A specific degradation of mutant transcript during or after pre-mRNA splicing is suggested.
General note: The following inbred strains are known to be homozygous for Pde6b: C3H sublines, CBA/J, FVB/NJ, PL/J, SB, SJL/J, and SWR/J.

Allele

Symbol: Adgrv1^frings
Name: Frings
MGI accession ID: MGI:2389570
Generation method: Spontaneous
Marker symbol: Adgrv1
Marker name: adhesion G protein-coupled receptor V1
Chromosome: 13
Strain of origin: various
Molecular note: The phenotype of the Frings mouse has been attributed to a single nucleotide deletion (guanine 7009) that results in a nonsense mutation in exon 27 (codon 2072). The stop codon putatively precludes translation of a multicopper oxidase (MCOI) consensus site in all three splice variants. The allele was originally described in RB/1 strain, but subsequently the same mutation was found in BUB/BnJ strain but not in 11 other strains of Swiss albino mice.

Allele

Symbol: Mx1^s1
Name: myxovirus susceptibility 1
MGI accession ID: MGI:3715154
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: Many 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.
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).

Allele

Symbol: Cox7a2l^l
Name: long
MGI accession ID: MGI:6276121
Generation method: Not Applicable
Attributes: Not Specified
Marker symbol: Cox7a2l
Marker name: cytochrome c oxidase subunit 7A2 like
Chromosome: 17
Strain of origin: multiple strains
Molecular note: This allele encodes the long isoform with 113 amino acids. It is found in 129S2/SvPasCrl, CBA/CaOlaHsd, Hsd:ICR, and NZB/OlaHsd.
General note: Querying the sequences of the Sanger Mouse Genomes Project reveals that the short allele with its 6 bp deletion exists in C57BL/6J, C57BL/10J, C57BL/6NJ, C58/J, BALB/cJ, C3H/HeH, 129S5/SvEvBrd, NZW/LacZ, and SEA/GnJ, but the long allele lacking the deletion exists in 129S1/SvImJ, A/J, AKR/J, BTBR T⁺ Itpr3^tf/J, BUB/BnJ, C3H/HeJ, C57BR/cdJ, C57L/J, CAST/EiJ, CBA/J, DBA/1J, DBA/2J, FVB/NJ, I/LnJ, KK/HiJ, LEWES/EiJ, LP/J, MOLF/EiJ, NOD/ShiLtJ, NZB/BlNJ, NZO/HlLtJ, PWK/PhJ, RF/J, SPRET/EiJ, ST/bJ, WSB/EiJ, ZALENDE/EiJ.

Allele

Symbol: Hbb^d
Name: d
MGI accession ID: MGI:1858119
Generation method: Not Applicable
Marker symbol: Hbb
Marker name: hemoglobin beta chain complex
Chromosome: 7
Strain of origin: BALB/c

Allele

Symbol: B2m^a
Name: a variant
MGI accession ID: MGI:6357680
Generation method: Spontaneous
Attributes: Not Applicable
Marker symbol: B2m
Marker name: beta-2 microglobulin
Chromosome: 2
Strain of origin: multiple strains
Molecular note: The a variant is slightly slower running on SDS PAGE and was found to have an aspartic acid at amino acid position 85. This allele is found in A, BALB/c, LP and most other strains.