P/J

Stock number: 000679
Research areas: Cancer Research, Dermatology Research, Developmental Biology Research, Hematological Research, Mouse/Human Gene Homologs, Neurobiology Research, Sensorineural Research

Description

P/J mice exhibit a high incidence of lymphatic leukaemia. They also show a high susceptibility to audiogenic and electroconvulsive seizures. P/J mice are also homozygous for a number of other mutations including nonagouti (a), brown (Tyrp1^b), pink-eyed dilution (Oca2^p), short ear (Bmp5^se), dilute Myo5a^d), and retinal degeneration 1 (Pdeb1^rd1

Detailed description

P/J mice exhibit a high incidence of lymphatic leukaemia. They also show a high susceptibility to audiogenic and electroconvulsive seizures. P/J mice are also homozygous for a number of other mutations including nonagouti (a), brown (Tyrp1^b), pink-eyed dilution (Oca2^p), short ear (Bmp5^se), dilute Myo5a^d), and retinal degeneration 1 (Pdeb1^rd1).

Development

The P/J inbred strain was created by G.D. Snell by extracting the genes a, Tyrp1^b (originally b), Myo5a^d (originally d), Bmp5^se (originally se), Oca2^p (originally p), Pde6b (originally rd) from strain BDP, developed by W. H. Gates, following an outcross.

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: Myo5a^d
Name: dilute
MGI accession ID: MGI:1856004
Generation method: Spontaneous
Marker symbol: Myo5a
Marker name: myosin VA
Chromosome: 9
Strain of origin: old mutant of the mouse fancy
Molecular note: This mutation is the result of the integration of ecotropic murine leukemia virus Emv-3 into a noncoding region of the Myo5a^d gene. Reversions of Myo5a^d to wild-type are caused by excision of the virus leaving exactly one long terminal repeat in place.

Allele

Symbol: Bmp5^se
Name: short ear
MGI accession ID: MGI:1856150
Generation method: Spontaneous
Marker symbol: Bmp5
Marker name: bone morphogenetic protein 5
Chromosome: 9
Strain of origin: mice from Abbie Lathrop mouse farm
Molecular note: The C to T substitution creates a stop codon at arginine codon 208 (p.R208*). The resulting truncated protein does not include the carboxy terminal signaling portion of the molecule.
General note: Phenotypic Similarity to Human Syndrome: Ear, Patella, Short Stature Syndrome (Meier-Gorlin Syndrome) in homozygous mice (J:24474)

Allele

Symbol: Gpr84^del
Name: deletion
MGI accession ID: MGI:5812913
Generation method: Spontaneous
Attributes: Null/Knockout
Marker symbol: Gpr84
Marker name: G protein-coupled receptor 84
Chromosome: 15
Strain of origin: multiple strains
Molecular note: This spontaneously arising frameshift deletion is located in exon 2 at position 103308576 bp (NCBI Build 37) and results in a premature stop codon. The mutation is predicted to result in a truncated protein lacking the transmembrane domains 4-7. The inbred strains BDP/J, DBA/1J, DBA/2J, I/LnJ, FVB/NJ, LG/J, MRL/MpJ, NODShi/LtJ, NOR/LtJ, P/J, PL/J, SKHIN/Sprd, SJL/J, SM/J are homozygous for the deletion. The allele is segregating in the outbred stocks ICR and CD-1.

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: H2^p
Name: p variant
MGI accession ID: MGI:5751521
Generation method: Not Applicable
Marker symbol: H2
Marker name: histocompatibility-2, MHC
Chromosome: 17
Strain of origin: various
Molecular note: The p haplotype of the H2 complex is known to be present in the inbred strains F/St, NB, and P/J.

Allele

Symbol: H2-T18^e
Name: e variant
MGI accession ID: MGI:4820511
Generation method: Not Applicable
Marker symbol: H2-T18
Marker name: histocompatibility 2, T region locus 18
Chromosome: 17
Strain of origin: Not Applicable
Molecular note: The allele H2-T18^e determines presence of specificities TL.1, 2, 3, 5 and occurs in strains P/J and BDP/J.

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