A/J

Stock number: 000646
Product name: AJ
Strain synonyms: A
Research areas: Cancer Research, Cardiovascular Research, Developmental Biology Research, Immunology, Inflammation and Autoimmunity Research, Internal/Organ Research, Mouse/Human Gene Homologs, Neurobiology Research, Research Tools, Sensorineural Research

Description

A/J inbred mice are widely used to model cancer and for carcinogen testing given their high susceptibility to carcinogen-induced tumors. Other uses include hybridoma production for immunology applications, cardiovascular research, developmental biology (low background incidence of cleft palate; high susceptibility to cortisone-induced cleft palate) and sensorineural given their early hearing loss.

Our preclinical efficacy testing services offer scientific expertise and an array of target-based and phenotype-based outcome measures, both in vivo and at endpoint, for flexible study designs and assay development in mouse models of muscular dystrophy. See our full service platform.

Detailed description

Developed by LC Strong in 1921 from a cross between a Cold Spring Harbor albino and a Bagg albino, the A/J inbred strain is widely used in cancer and immunology research. It is highly susceptible to cortisone-induced congenital cleft palate. It has a high incidence of spontaneous lung adenomas, and lung tumors readily develop in response to carcinogens. A high percentage of mammary adenocarcinomas (a large proportion of acinar-type) develop in multiparous females. Rare spontaneous myoepitheliomas arising from myoepithelial cells of various exocrine glands have been observed in The Jackson Laboratory substrains. A/J are much less responsive to LPR than are C57BL/6J, generating less IL10 and having lower mortality. Fulton et al. (2006) mapped this trait to an interval containing Msr1 and found lower MSR1 expression on A/J peritoneal macrophages. Compared with MRS1 from C57BL/6J, A/J MRS1 has a faster electrophoretic mobility and polymorphisms that impact N-linked glycosylation.

A/J mice fed an atherogenic diet (1.25% cholesterol, 0.5% cholic acid, and 15% fat) fail to develop atherosclerotic aortic lesions in contrast to several highly susceptible strains of mice (e.g. C57BL/6J, Stock No. 000664; C57L/J, Stock No. 000668, C57BR/cdJ, Stock No. 000667, and SM/J, Stock No. 000687). In addition to atherosclerosis resistance, A/J mice are resistant to diabetes, obesity, insulin resistance and glucose intolerance. On either chow or high fat diet, A/J mice maintain low glucose and insulin levels.

A/J mice develop cigarette smoke-induced emphysema in approximately half the time when compared with C57BL/6J mice. Structural lung damage caused by induced asthma mimics the phenotype found in asthma patients more closely than does the induced damage in BALB/c mice.

A strain characteristic of A/J is a late onset (four to five months) progressive muscular dystrophy as a result of a homozygous retrotransposon insertion in the dysferlin (Dysf) gene. Myofibers in Dysf^prmd homozygotes undergo degeneration and regeneration, and their nuclei are placed centrally. Proximal muscles are more severely affected than distal muscles (Ho M, et al. 2004).

Sequencing of the mitochondrial genome of A/J reveals 10 adenines in a polymorphic adenine repeat sequence in the mt-Tr sequence. This repeat contains nine adenines in NOD/ShiLtJ, A/HeJ, A/WySnJ, and SKH2/J and 10 adenines in A/J, and NZB/B1NJ, and likely enhances the hearing loss associated with the Cdh23^ahl allele (Johnson et al. 2001).

A/J mice are challenging breeders, exhibiting reduced productivity and high incidence of non-productive matings. They may require some special maintenance. A/J mice tend to be very docile and easy to work with.

Development

In 1921 LC Strong crossed a Bagg albino with a Cold Spring Harbor albino stock, maintained by Little, to begin the A/St strain. In 1928 breeders were sent to Arthur Cloudman and subsequent to the 1947 Bar Harbor fire survivors at generation F73 founded The Jackson Laboratory A/J strain. This strain reached generation F217 in 1990, and F270 in 2006.

Allele

Symbol: Cs^ahl4
Name: age related hearing loss 4
MGI accession ID: MGI:3807581
Generation method: Spontaneous
Attributes: Not Specified
Marker symbol: Cs
Marker name: citrate synthase
Chromosome: 10
Strain of origin: A/J
Molecular note: The C-to-A nucleotide change in exon 3 of A/J (SNP rs29358506) mice causes a nonconservative amino acid change, from histidine (H) to asparagine (N) at position 55 of the protein (p.H55N). This histidine is highly conserved in the orthologous proteins of all mammals and in many other species indicating that it is likely to be functionally important. A/WySnJ and A/HeJ contain a C at this SNP.
General note: This mutation likely occurred in the A/J lineage between 1928 and 1975. J:188196

Allele

Symbol: Micrlⁿ
Name: non-responder
MGI accession ID: MGI:5014256
Generation method: QTL
Marker symbol: Micrl
Marker name: microwave induced increase in complement receptor B cells
Chromosome: 5
Strain of origin: multiple strains
General note: The following inbred strains are homozygous for the recessive QTL, Micrl, and do not respond to microwave exposure by increasing splenic C3 receptor-bearing B cells: A/J, BALB/cJ, C3HeB/FeN, C57BL/6J, C57BL/10J (inferred from the response of two congenic lines "B10.BR", "B10.D2", "B10.D2"), C58/J, AK.B6-H2^b, and B6.AK-H2^k. These recombinant inbred strains are also non-responding: BXH2/Ty, BXH6/Ty, BXH7/Ty, BXH12/Ty, and BXH14/Ty.

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: Nrg3^ska
Name: scaramanga
MGI accession ID: MGI:1889610
Generation method: Spontaneous
Marker symbol: Nrg3
Marker name: neuregulin 3
Chromosome: 14
Strain of origin: A/J
Molecular note: This allele maps to an interval between the microsatellite markers D14Mit14 and D14Mit80 located at 10.0 cM and 13.5 cM. The mutation identified is a microsatellite repeat within intron 7 of the gene. This simple sequence repeat (SSR) was found to completely cosegregate with the ska phenotype.

Allele

Symbol: Rmcf^s
Name: MCF sensitive
MGI accession ID: MGI:3798962
Generation method: Spontaneous
Marker symbol: Rmcf
Marker name: resistance to MCF virus
Chromosome: 5
Strain of origin: multiple strains
Molecular note: This locus controls resistance of cells to infection by mink cell focus-forming murine leukemia viruses. The recessive s (susceptible) allele is found in AKR/J, C57BL/6, BALB/c, CBA/J, NFS, NZB and 129/J.
General note:

This locus controls resistance and susceptibility of cells in tissue culture to infection by mink cell focus-forming murine leukemia viruses. The allele Rmcf^r determines resistance and occurs in strains DBA/1, DBA/2, and CBA/Ca; the allele Rmcf^s determines susceptibility and occurs in strains AKR/J, C57BL/6, BALB/c, CBA/J, NFS, NZB, 129/J, and many others. Heterozygotes are as resistant as the resistant parent or nearly so. Rmcf is different from and independent of Fv1, a locus that controls susceptibility to infection by ecotropic viruses. Rmcf is located on Chr 5 close to Hm near the centromeric end (J:7108). Rmcf^r protects (AKR x CBA/Ca)F1 and (AKR x DBA/2)F1 hybrids from development of spontaneous thymic lymphomas and reduces the incidence of MCF-induced thymic lymphomas (J:7175). It also reduces susceptibility of cells of Sxv^s/Sxv^r mice to exogenous xenotropic viruses (J:7951). In addition, in strains susceptible to Friend virus-induced erythroleukemia, a condition thought to be due to the replication of MCF virus, Rmcf^r increases resistance to the virus-induced erythroleukemia. It may cause resistance by coding for or regulating the production of an MCF-related envelope glycoprotein that blocks the receptor for MCF viruses (J:8074). This conclusion is reinforced by the findings of Buller et al. (J:8497), who showed that the Rmcf^r allele contains an endogenous MCF gp70 env gene and that the Rmcf^s allele, at least in some strains (C57BL/6, CBA/J, and A/WySn), contains a xenotropic gp70 env gene. Presumably the MCF gp70 inhibits exogenous MCF infection in vitro by a mechanism of viral interference.

Allele

Symbol: Hc⁰
Name: deficient
MGI accession ID: MGI:3027637
Generation method: Spontaneous
Marker symbol: Hc
Marker name: hemolytic complement
Chromosome: 2
Strain of origin: multiple strains
Molecular note: A 2 base "TA" deletion at positions 62 and 63 of an 83 base pair exon near the 5' end of the gene is found in the following mouse strains: A/HeJ, A/J, AKR/J, DBA/2J, I/LnJ, KK/HlJ, MOLF/EiJ, NZB/B1NJ, RF/J, ST/bJ SWR/J, B10.D2/oSnJ. The consequence of this deletion is the creation of a stop codon starting four bases after the deletion. A truncated product of 216 amino acids is predicted as a result although contradictory reports exist that a larger pro-C5 protein may be synthesized. Nevertheless, macrophages from mouse strains carrying this allele do not secrete complement 5.
General note:

This is an allele characteristic of various inbred mouse strains including the following: A/HeJ, A/J, AKR/J, DBA/2J, NZB/B1NJ, SWR/J, B10.D2/oSnJ

Hc was identified as a candidate gene for Abhr2 in a microarray analysis of lung mRNA from A/J, C3H/HeJ, and (A/J x C3H/HeJ)F1 x A/J backcross animals. Hc genotype shows statistically significant correlation to allergen-induced bronchial hyperresponsive phenotype. The A/J allele contains a 2 bp deletion resulting in deficient Hc mRNA and protein production and is associated with susceptibility to allergen-induced bronchial hyperresponsiveness. (J:108211)

Allele

Symbol: Wnt9b^clf1
Name: cleft lip 1
MGI accession ID: MGI:1856821
Generation method: Spontaneous
Marker symbol: Wnt9b
Marker name: wingless-type MMTV integration site family, member 9B
Chromosome: 11
Strain of origin: A/WySn
Molecular note: This mutation is a novel insertion of an IAP transposon 3' from the gene. In addition, a standard genetic test of allelism between clf1 and a Wnt9b targeted mutation demonstrated noncomplementation, showing clf1 is an allele of Wnt9b.
General note: Unequal duplicate epistasis - the normal allele at clf1 is a dominant suppressor of the recessive phenotype at clf2, and the normal allele at clf2 is a semidominant suppressor of the recessive phenotype at the clf1 locus.

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: mt-Tr^m1
Name: mutation 1
MGI accession ID: MGI:3831887
Generation method: Spontaneous
Marker symbol: mt-Tr
Marker name: mitochondrially encoded tRNA arginine
Chromosome: MT
Strain of origin: various
Molecular note: The adenine repeat in the D stem is polymorphic with 10 adenines in this allele.
General note: This polymorphism is present in A/J, NZB/B1NJ, ALS/Lt and NOD/ShiLtJ. A variant with 9 adenines is found in NOD/ShiLtDvs, ALR/Lt and SKH2/J.

Allele

Symbol: Naip5^Lgn1-s
Name: Legionella, susceptiblility 1
MGI accession ID: MGI:3769036
Generation method: Spontaneous
Marker symbol: Naip5
Marker name: NLR family, apoptosis inhibitory protein 5
Chromosome: 13
Strain of origin: A/J
Molecular note: A/J mice are susceptible to infection by Legionella pneumophilia. This susceptibility is heritable and is caused by a polymorphism in the Naip5 gene. Expression of BAC clones containing the Naip5 gene from resistant strains (C57BL/6J and 129X1/SvJ) in A/J mice rendered transgenic mice resistant to infection (J:81887, J:129300). In addition, Western blot experiments demonstrated that the NAIP5 protein is not expressed in A/J macrophages, while robust expression is seen in macrophages from resistant strains such as C57BL/6J. Sequence polymorphisms in this gene between susceptible and resistant strains were identified that may account for the difference in phenotype. In addition, morpholino antisense inhibition of NAIP5 activity in mouse macrophages from resistant mice resulted in an increase in permissiveness of Legionella replication (J:129300).

Allele

Symbol: Dysf^prmd
Name: progressive muscular dystrophy
MGI accession ID: MGI:3055150
Generation method: Spontaneous
Attributes: Null/Knockout
Marker symbol: Dysf
Marker name: dysferlin
Chromosome: 6
Strain of origin: A/J
Molecular note: A retrotransposon insertion occurred within intron 4, causing aberrant splicing of the gene. Protein was abolished as shown by Northern blot and immunoblot analysis. The insertion was 6000bp in size. This allele was found only in A/J mice, not in A/WySnJ, A/HeJ, C57BL/6J, SJL/J, SWR/J or 129/SvJ mice.

Allele

Symbol: Bhr5^A/J
Name: A/J
MGI accession ID: MGI:2156474
Generation method: QTL
Marker symbol: Bhr5
Marker name: bronchial hyperresponsiveness 5
Chromosome: 6
Strain of origin: A/J
Molecular note: This allele confers susceptibility to airway hyperresponsiveness compared to C3H/HeJ.
General note: Heterozygosity for A/J-derived alleles at both Bhr1 and Bhr5 is sufficient to confer the airway hyperresponsive phenotype.

Allele

Symbol: Bhr1^A/J
Name: A/J
MGI accession ID: MGI:2155212
Generation method: QTL
Marker symbol: Bhr1
Marker name: bronchial hyperresponsiveness 1
Chromosome: 2
Strain of origin: A/J
Molecular note: This allele confers increased airway hyperresponsiveness compared to C57BL/6J.
General note: Heterozygosity for A/J-derived alleles at both Bhr1 and Bhr5 is sufficient to confer the airway hyperresponsive phenotype.

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: 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.