Mouse Diseases Common Conditions (phenotypes) and Infectious Diseases TABLES only TABLES - Table number corresponds to section in TEXT Table Ia Table Ib Table Ic Common conditions by age Common conditions or phenotypes by strain Some immune relevant genotypes (in common strains) Page 2 Table Id Table Ie Table If Table Ig Table Ih Table Ii Immunodeficient mice: Properties of important genes & mutations Immunodeficient mice: Effects of Background strain on phenotypes Immunodeficient mice: Primary T cell deficient options Immunodeficient mice: MORE nude options Immunodeficient mice: MORE scid options Immunodeficient mice: MORE options Page 5 Table II Infectious Agents by site/system Table IV Viruses – Test methods, prevalence Table V Bacteria – Test methods, prevalence Table VI Eukaryotes – Test methods, prevalence Table VIa Protozoa by site Table VIb Fur mite comparison Table VIc Pinworm comparison Page 9 WEB Resources References Page 14 TEXT SECTIONS see also [1] Common disease conditions – Spontaneous or Non infectious Common diseases – Infectious by system Infectious agents, diagnostic methods Infectious agents, Viruses 1. Comments by agent (alphabetical order) V Infectious agents, Bacteria 1. Comments by agent (alphabetical order) VI Infectious agents, Eukaryotes 1. Fungi – inc Protista – Comments by agent (alphabetical order) 2. Protozoa – Comments by agent (alphabetical order) Metazoa - Comments by agent (alphabetical order) a) Arthropods Comments by agent (alphabetical order) b) Helminths Comments by agent (alphabetical order) I II III IV cbrayton@jhmi.edu 2013 Page 1 of 14 Mouse Diseases Common Conditions (phenotypes) and Infectious Diseases TABLES only Table Ia: Non infectious CLINICAL conditions in mice at different ages [2] [3] [4] Usually young mice Life threatening Hydrocephalus Malocclusion Usually not life threatening Microphthalmia Usually adult, various ages Dermatitis and wounds Abdominal enlargement (e.g. hydrometra, hydronephrosis, urinary obstruction, ascites). ‘Neurologic’ signs (e.g. paresisparalysis, seizures, vestibular signs) Alopecia due to barbering Blind / deaf Usually older mice Neoplasia (tumors) Wasting due to chronic progressive conditions (e.g. amyloidosis, nephropathy, neoplasia) Obesity Table Ib. Non infectious conditions and neoplasms in common mouse strains [2] [3] [4] [5] 129 strains A/J AKR BALB/c BALB/cBy C3H C57BL/6 DBA FVB/N Acallosity-hypocallosity; acidophilic macrophage pneumonia, hyalinosis Lung tumors (testicular teratomas) Congenital anomalies; amyloidosis; muscular dystrophy Lung tumors, rhabdomyosarcoma [6] Thymic lymphoma Acallosity-hypocallosity; conspecific (male) aggression; cardiac calcinosis; cardiac thrombi; vaginal septa Lung tumors; Harderian gland tumors; myoepithelioma; rhabdomyosarcoma, induced plasmacytoma Blind (rd1/rd1); cardiac calcinosis, soft tissue mineralization Mammary tumors in females; liver tumors in males Hydrocephalus; microphthalmia; ulcerative dermatitis; amyloidosis; acidophilic macrophage pneumonia, hyalinosis Lymphoma; histiocytic sarcoma dba, Cardiac calcinosis, soft tissue mineralization; seizures; deafness; glaucoma BLIND rd1 Blind (rd1/rd1); seizures; mammary hyperplasia Lung tumors Diabetes; immune alterations Lymphoma Blind (rd1/rd1); conspecific (male) aggression; muscular dystrophy Radioresistant Lymphoma Strain stock variations in: blind due to rd1/rd1; acidophilic macrophage pneumonia; amyloidosis; nephropathy; urinary syndrome Lymphomas; lung tumors; liver tumors; skin tumors C3H, CBA, FVB, SJL, SWR etc DEAF C57BL/6, BALB, DBA, etc NOD SJL/J Swiss Not inbred Re tumor frequency – see also http://tumor.informatics.jax.org/mtbwi/index.do cbrayton@jhmi.edu 2013 Page 2 of 14 Mouse Diseases Common Conditions (phenotypes) and Infectious Diseases TABLES only Table Ic: Some immune relevant genotype variations (in common strains) [7] Gene symbol H2 Gene /Locus name Chrom Allele name 17 Allele Symbol a H2 Major Histocompatibility Complex (MHC) H2 haplotypes MHC H2 haplotype H2 H2a * A (A/HeJ, A/J, AWySnJ) 17 b H2b MHC H2 haplotype 17 b2 H2b2 C57BL/6, C57BL/10 129 - all? NZB H2 MHC H2 haplotype 17 d H2d H2 MHC H2 haplotype 17 g7 H2g7 H2 MHC H2 haplotype 17 k H2k H2 MHC H2 haplotype 17 P H2p AKR, C3H, CBA, MRL P H2 MHC H2 haplotype 17 q H2q DBA/1, FVB/N, Nu/J H2 MHC H2 haplotype 17 r H2r RIII H2 MHC H2 haplotype 17 s, s2 H2s,s2 SJL, SJL/J H2 MHC H2 haplotype 17 z H2z Hc Hemolytic complement (c5) 2 0 (Hc0) 0 = deficient 2 base "TA" deletion Tlr4 Toll like receptor 4 4 Lps-d (Tlr4Lps-)d Rmcf MCF sensitive 5 s (Rmcfs) d = defective lipopolysaccharide response s = sensitive to mcf forming leukemia viruses C to A substitution in 3rd exon recessive Rmcf MCF sensitive 5 Ceacam1 carcinoembryonic antigen-related cell adhesion molecule 1 killer cell lectin-like receptor, subfamily A1 (aka Ly49A) Aka Ly49B 7 R (Rmcfr) Hc2-r (Ceacam1 Hv2-r) Resistant to mcf forming leukemia viruses r = resistance to Mouse hepatitis virus (MHV-4) Klra1 Inhibit killing activity [8] Dominant allele Deletion 23 aa substitution recessive Various B6, NOD, 129, BALB/c Inhibit killing activity [8] Various B6, 129, BALB/c Inhibit killing activity [8] Various B6, NOD, BALB/c Inhibit killing activity [8] Various Various Klra1 (Ly49a) Klra2 6 Mutation Strains DBA/2 BALB/c, BALB/cBy, NOD NZW, NZN, NZO A/HeJ, AKR/J, DBA/2J, FVB/N; NZB/B1NJ, SWR/J, B10.D2/SnJ C3H/HeJ AKR/J, C57BL/6, BALB/c, CBA/J, NFS, NZB, 129/J. DBA/1, DBA/2, and CBA/Ca SJL/J C57BL/6 6 etc Klra2 C57BL/6 etc Klra3 Aka Ly49C 6 Klra3 C57BL/6 etc Klra5,6,9,1 5,17,19, 20,21,22 * Aka Ly49E,F,I,O, Q,S,T,V 6 See also http://jaxmice.jax.org/literature/catalog/mhc_h2_haplotypes.pdf http://www.imgt.org/IMGTrepertoireMHC/Polymorphism/haplotypes/mouse/MHC/Mu_haplotypes.html cbrayton@jhmi.edu 2013 Page 3 of 14 Mouse Diseases Common Conditions (phenotypes) and Infectious Diseases TABLES only Gene symbol Klra4,8, 13,14,16, 18,21,23, 25,28,30 Mx1 Mx1 Mx1 Tcrb-V8 Tcrb-V8 Nlrp1a Gene /Locus name Chrom Allele Symbol Allele name Mutation Strains Aka Ly4D,H,M, N,P,R,U,W 6 Activate NK etc [8] Various Various myxovirus (influenza virus) resistance 1 myxovirus resistance 1 16 Mx1 r Wild type A2G, SL/NiA, CAST/Ei Mx1 s1 r = resistance to Myxovirus (etc intranuclear virus ) [9] s1 = susceptibility 1 [10] 16 deletion 16 Mx1 s2 s2 = susceptibility 2 [10] 6 Tcrb-V8 a A = wild type Point mutation Wild type 6 Tcrb-V8 c Most common strains C57BL/6J, C3H/HeJ, BALB/cJ,etc CBA/J, CE/J, I/LnJ, PERA/Ei A/J, AKR/J, BALB/cJ, C3H/HeJ, C57BL/10J, C57BL/6J, MRL C57L/J, SJL/J myxovirus resistance 1 T cell receptor beta, variable 8 T cell receptor beta, variable 8 NOD-like receptor (NLR) 1a 11 Nlrp1aR/R Nlrp1a NOD-like receptor (NLRs) 1a 11 Nlrp1as/s Slc11a1 (Nramp1) solute carrier family 11 member 1; host resistance 1 Slc11a1 r Slc11a1 (Nramp1) solute carrier family 11 member 1; pathogen susceptibility 1 Slc11a1 s deletion Resistance to anthrax LT lethal toxin [11] NLRs = inflammasome components Sensitivity to anthrax LT lethal toxin [11] r = resistance to certain agents – some Mycobacterium sp, S. typhimurium, L donovani [12] s = susceptibility to certain agents – some Mycobacterium sp, S. typhimurium, L donovani [12] dominant allele (wild type?) G to A point mutation recessive C57BL/6J, A/J, I/LnJ, SPRET/EiJ, PWK/PhJ, PWD/PhJ, AKR/J, NOD/LtJ, DBA/2J 129S1/SvlmJ, Balb/cJ, FVB/NJ, SWR/J, CAST/EiJ, C57/LJ A; C3H; CBA; DBA [12] C3H/HeJ, 129/Sv BALB/c; C57BL [12] Search for gene/locus/allele updates at http://www.informatics.jax.org/ Search for mice at http://www.findmice.org/index.jsp cbrayton@jhmi.edu 2013 Page 4 of 14 Mouse Diseases Common Conditions (phenotypes) and Infectious Diseases TABLES only Table Id: Immunodeficient mice: properties of important genes & mutations Gene B2m beta-2 microglobulin PROPERTIES Required for normal expression of major histocompatibility class I proteins (displaying viral and self antigens to potentially responsive T cells) and for CD8+ T cell maturation and NK cell development Tm Deficiency NK cell development/activity, CD8+ T cell activity Foxn1 forkhead box N1, formerly Hfh11 nu mutation known as nude. nu/nu are ‘hypothymic’ – ‘athymic’ T cell deficient; respond poorly to thymus-dependent antigens, should accept allogeneic and xenogeneic grafts(but may have NK activity & be leaky) Greatly increased susceptibility to infection. Il2rg interleukin 2 receptor, gamma chain Necessary for IL2, IL4, IL7, IL9, IL15, IL21 high affinity binding & signaling. Role in mediating susceptibility to thymic lymphomas in mice Myd88 myeloid differentiation primary response gene 88 Tm Deficiency NO NK development +other defects in innate immunity. NO thymic lymphomas on susceptible background Myd88 is an adapter protein used by all TLRs (except TLR 3) to activate transcription factor NF-κB in innate immunity Tm Deficiency innate responses – neutrophils, macrophages, hematopoietic, molecular signaling, and apoptotic abnormalities Prf1 perforin 1 (pore-forming protein) Essential in lytic pathway by which NK and CD8+ lymphocytes kill targeted cells. Prkdc protein kinase, DNA-activated, catalytic polypeptide Involved in repairing double-stranded DNA breaks and in recombining the variable (V), diversity (D), and joining (J) segments of immunoglobulin and T-cell receptor genes. scid mutation/allele ‘severe combined immunodeficient’ Rag1 recombination activating gene 1 Ticam1 Trif Tm Deficiency NK cell activity, CD8+ T cell activity scid/scid no mature T and B cells, cannot mount cell mediated or humoral adaptive immune responses, do not reject allogeneic and xenogeneic grafts, useful cancer research models. BUT leakiness some functional B and T cells as they age. leakiness in non-SPF conditions, leakiness C57BL/6J, BALB/cByJ backgrounds > C3H/HeSnJSmn > NOD/LtSzJ background ++ radiosensitive cannot be as thoroughly irradiated as other immunodeficient models before being engrafted renders NOD mice diabetes-free useful for adoptive transfer of diabetes by T cells. Essential for V(D)J gene rearrangements necessary functional antigen receptors in T & B cells. Deficient tm1Mom mutants no mature, functional T and B cells. Renders NOD mice diabetes-free. + B cell lymphomas in NOD.129S7(B6)-Rag1tm1Mom/J Toll-like receptor adaptor molecule 1 (formerly uses TIR-domain–containing adapter-inducing interferon-b (TRIF)). adapter protein used by TLR 3 to activate transcription factor NF-κB in innate immunity Tm Deficiency innate responses – esp when combined with Myd88 Tm Tm = targeted mutation (knockout) cbrayton@jhmi.edu 2013 Page 5 of 14 Mouse Diseases Common Conditions (phenotypes) and Infectious Diseases TABLES only Table Ie: Immunodeficient mice: Effects of Background strain on phenotypes adapted from Jaxnotes #501, 2006 [13] http://jaxmice.jax.org/jaxnotes/archive/501.pdf etc Back ground Innate NK etc Leaky H2 Examples ‘common name’ Characteristics (Phenotypes) BALB Substrains Normal Yes T d CByJ.Cg-Foxn1nu/J ‘BALB/c Nude’ Normal B cells etc Extra thymic T cells with age POOR breeders, female fertility nu/+ F x nu/nu M Normal High d CBySmn.CB17Prkdcscid/J ‘BALB/c scid’ NO functional B and T cells HIGH NK, complement activity (normal APC function) Thymic lymphomas but < NOD.CB17-Prkdcscid/SzJ RadioSensitive Normal NO b B6.129S7Rag1tm1Mom/J ‘B6 Rag’ NO functional B and T cells HIGH NK activity (normal APC, complement c5) Normal High b B6.CB17Prkdcscid/SzJ ‘B6 scid’ NO functional B and T cells HIGH NK, complement activity (normal APC function) Low NO g7 NOD/ShiLtJ ‘NOD’ susceptible to immune mediated insulitis + diabetes NK, macrophage, APC activity; Hc0 No c5 RadioResistant Low NO g7 NOD.129S7(B6)Rag1tm1Mom/J ‘NOD Rag’ NO functional B and T cells Pre-B cell > Thymic lymphomas ( 10.5mo) Somewhat RadioResistant Low NO g7 NOD.Cg-Rag1tm1Mom Prf1tm1Sdz/SzJ ‘NOD Rag Prf’ NO functional B and T cells, NO NK cell activity; Hc0 No c5 Thymic lymphomas (short lifespan ~8.5mo) RadioResistant: survives up to 8 Gy Low Low g7 NOD.CB17Prkdcscid/J NO functional B and T cells NOD background low NK activity, Hc0 No c5, defects in myeloid development, poor APC functions Thymic lymphomas (short lifespan ~8.5mo) RadioSensitive: tolerates up to 4 Gy Low Low g7 NOD.Cg-Prkdcscid B2mtm1Unc/J ‘NOD scid B2m’ NO functional B and T cells No MHC 1 expression ~NO NK activity Thymic lymphomas (short lifespan ~6.3mo) Hemochromatosis dt? Low NO g7 NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ ‘NSG’ NO lymphocytes; NO NK cell activity Lymphoma-resistant; long-lived > 16m JAX Low NO NOD.Cg-Prkdcscid Il2rgtm1Sug/JicTac ‘NOG’ NO lymphoctes; NO NK cell activity Lymphoma-resistant; long-lived > 16m TAC Normal Yes T NU/J NIH outbred nude stock inbred at TJL C57BL/6J NOD NIH stock cbrayton@jhmi.edu 2013 q (Foxn1nu) Page 6 of 14 Mouse Diseases Common Conditions (phenotypes) and Infectious Diseases TABLES only Table If: Immunodeficient mice: Primary T cell deficient options T Cells B Cells Innate NK Leaky Foxn1nu (nude) D N N yes Prkdcscid (scid) D D N- yes Thymic lymphoma PrkdcscidLystbg (scid-bg) D D N Reduced by bg Thymic lymphoma NOD-Prkdcscid (NOD-scid) D D D Minimal Thymic lymphoma NOD, Prkdcscid, Il2rgtm… (NSG, NOG) D D D No Mutations Tumors D = Deficient, N = ‘normal’ Table Ig: Immunodeficient mice: MORE NUDE options Source Background Name INbred AKA Tac Bom B6N/Tac B6.Cg/NTac-Foxn1nu + B6 nude BALB/cAnN C.Cg/AnNTac-Foxn1nu + BALB/c nude BALB/cBom C.Cg/AnBomTac-Foxn1nu + BALB/cA nude BALB x NIH(S) CrTac:NCr-Foxn1nu NIH Nude NMRI (S) BomTac:NMRI-Foxn1nu Swiss nude NIH(S) NTac:NIHS-Foxn1nu Swiss Nude BALB/cAnN CAnN.Cg-Foxn1nu/Crl CD1 (S) Crl:CD1-Foxn1nu CD1 nude NIH Nu Crl:NU-Foxn1nu Nu/nu NIH nude NIH Nu Hsd:Athymic Nude-Foxn1nu NIH nude NMRI (S) HsdCpb:NMRI-Foxn1nu Swiss Nude CD1 (S) HsdHli:CD1-Foxn1nu CD1 nude ICR (S) HsdOla:ICRF-Foxn1nu Swiss Nude MF1 HsdOla:MF1-Foxn1nu MF1 nude BALB/cOla BALB/OlaHsd-Foxn1nu Crl Hsd Ola cbrayton@jhmi.edu 2013 + + BALB/c Nude BALB nude Page 7 of 14 Mouse Diseases Common Conditions (phenotypes) and Infectious Diseases TABLES only Table Ih: Immunodeficient mice: MORE scid options Source Background Name INbred AKA Tac Bom C.B17 C.B-Igh-1b/IcrTac-Prkdcscid + CB17 scid IcrTac IcrTac:ICR-Prkdcscid C.B-17 C.B-Igh-1b/GbmsTac-Prkdcscid-Lystbg + scid-beige NOD + NOD/MrkBomTac-Prkdcscid + NODscid NOD NOD.Cg-Prkdcscid Il2rgtm1Sug/JicTac + CIEA NOG C.B17 CB17/Icr-Prkdcscid/IcrCrl + CB17 scid Crl Scid - Swiss Crl:SHO-PrkdcscidHrhr Hsd Ola Scid hairless outbred BALB/cJ BALB/cJHan™Hsd-Prkdcscid + BALB/c Scid C.B-17 C.B-17/IcrHsd-Prkdcscid + CB17 scid C3H C3H.C-Prkdcscid/IcrSmnHsd + C3H scid ICR (S) HsdIcr:Ha(ICR)-Prkdcscid NOD CB17 NOD.CB17/JHliHsd-Prkdcscid Scid + NODscid Table Ii: Immunodeficient mice: MORE options Source Background Name INbred AKA Tac Bom C.B17 C.B-Igh-1b/IcrTac-Prkdcscid + CB17 scid IcrTac IcrTac:ICR-Prkdcscid C.B-17 C.B-Igh-1b/GbmsTac-Prkdcscid-Lystbg + scid-beige NOD + NOD/MrkBomTac-Prkdcscid + NODscid NOD NOD.Cg-Prkdcscid + CIEA NOG C.B17 CB17/Icr-Prkdcscid/IcrCrl + CB17 scid Crl Il2rgtm1Sug/JicTac Scid - Swiss Crl:SHO-PrkdcscidHrhr Hsd Ola Scid hairless outbred BALB/cJ BALB/cJHan™Hsd-Prkdcscid + BALB/c Scid C.B-17 C.B-17/IcrHsd-Prkdcscid + CB17 scid C3H C3H.C-Prkdcscid/IcrSmnHsd + C3H scid ICR (S) HsdIcr:Ha(ICR)-Prkdcscid NOD CB17 NOD.CB17/JHliHsd-Prkdcscid cbrayton@jhmi.edu 2013 Scid + NODscid Page 8 of 14 Mouse Diseases Common Conditions (phenotypes) and Infectious Diseases TABLES only Table II Infectious agents in mice, listed by site or by primary disease phenotype when there are pathology findings Viruses ENTERIC-HEPATIC Calicivirus (MNV) Coronavirus (MHV) Reovirus 3 (Reo3) Rotavirus EDIM Bacteria ENTERIC-HEPATIC Citrobacter rodentium Escherichia coli Clostridium piliforme Cl difficile, Cl perfringens Helicobacters Salmonella enterica Ssp typhimurium Segmented Filamentous Bacteria (SFB) Eukaryotes ENTERIC-HEPATIC Fungi Gastric yeasts Protozoa Eimeria sp. Cryptosporidia Entamoebae Flagellates Nematodes Aspiculuris tetraptera Syphacia muris Syphacia obvelata RESPIRATORY Paramyxovirus (MPV,Sen) IMMUNE or MULTISYSTEM Adenovirus (MAV1,2) Arterivirus (LDV) Ectromelia virus (ECT) Herpesvirus (MCMV, MTV) LCM virus (LCMV) LDH virus (LDV) Papova (K, MPyV) Parvoviruses (MMV, MPV) CNS PicoRNAvirus (TMEV etc) OTHER Hantavirus (HAN) Retrovirus Papillomavirus cbrayton@jhmi.edu 2013 RESPIRATORY Bordetella avium, hinzii, etc, CAR bacillus Klebsiella pneumoniae Mycoplasma pulmonis Pasteurella pneumotropica SKIN (or abscesses) Corynebacterium bovis Corynebacterium kutscheri Staphylococcus aureus Staphylococcus species Streptobacillus moniliformis Bacteremia, Septicemia Klebsiella oxytoca etc spp Proteus mirabilis Pseudomonas aeruginosa Streptococcus, Enterococcus spp. OTHER Chlamydiae Mycobacterium spp Mycoplasmas Haemotrophic Cestodes Cysticercus fasciolaris Hymenolepis diminuta Rodentolepis microstoma Rodentolepis nana RESPIRATORY Fungi Pneumocystis murina SKIN/HAIR Fungi Dermatophytes Arthropods Lice Mites – Fur, Follicles OTHER Fungi Encephalitozoon cuniculi Protozoa Klossiella muris Sarcocystis muris Arthropods Mesostigmatid mites NON parasitic arthropods Psocids Page 9 of 14 Mouse Diseases Common Conditions (phenotypes) and Infectious Diseases TABLES only Table IV Viruses in mice: test methods and results from Pritchett-Corning, Cosentino, Clifford (2009) [14] (see also [15] [16] [17] [18]), and survey results from Carty 2008. [19] The most common agents are in boldface. The final column indicates if PCR testing is commercially available on feces (F) or biological materials (B) such as serum or cultured cells. Agent (common abbreviations) Primary test [14] Confirmatory test %Pos Results [14] [14] Adenoviridae MFIA/ IFA Mouse Adenovirus (MAV1, MAV2) ELISA Arenaviridae MFIA/ Lymphocytic choriomeningitis virus IFA ELISA (LCMV) Arteriviridae Lactate dehydrogenase-elevating virus Enzyme* PCR (LDHV, LDV) Caliciviridae MFIA/ IFA Murine norovirus (MNV) ELISA Coronaviridae MFIA/ IFA Mouse Hepatitis virus (MHV) ELISA Bunyaviridae MFIA/ IFA Hantavirus (HAN, HNT) ELISA Herpesviridae MFIA/ IFA Mouse Cytomegalovirus (MCMV) ELISA Herpesviridae IFA PCR Mouse Thymic virus (MTV, MTLV) Paramyxoviridae MFIA/ IFA, HAI Pneumonia virus of mice (PVM) ELISA Paramyxoviridae MFIA/ IFA, HAI Sendai virus (SEND, SEN) ELISA Parvoviridae MFIA/ IFA, HAI Parvovirus (MVM, MMV) ELISA Parvoviridae MFIA/ IFA Parvovirus (MPV 1,2) ELISA Picornaviridae (Cardiovirus) MFIA/ Theiler's murine encephalomyelitis virus IFA ELISA (TMEV, GD-VII) Polyomaviridae MFIA/ IFA Mouse Pneumonitis virus (K) ELISA Polyomaviridae MFIA/ IFA Polyoma virus (POLY) ELISA Poxviridae (Othopoxvirus) MFIA/ IFA Ectromelia virus (ECTRO, ECT)) ELISA Reoviridae MFIA/ IFA, HAI Reovirus (REO, REO3) ELISA Reoviridae MFIA/ IFA Mouse Rotavirus (EDIM, MRV) ELISA Abbreviations in the table – see also section diagnostic methods %Pos inst. [19] Comment 0.02 FB 0.01 Zoonotic B Chem B 32.3 1.6 PCR? FB >40% 0 FB Zoonotic 0.04 B B B 0.01 B 0 B 0.3 ~40% FB 1.8 >90% FB 0.26 FB 0 B 0.02 B 0.02 B 0.01 B 0.56 ~30% FB Chem – plasma chemistry test for elevated lactate dehydrogenase activity ELISA - Enzyme-linked immunosorbent assay IFA - Indirect immunofluorescence assay MFIA - multiplexed fluorometric immunoassay HAI - Hemagglutination inhibition assay PCR - Polymerase Chain reaction cbrayton@jhmi.edu 2013 Page 10 of 14 Mouse Diseases Common Conditions (phenotypes) and Infectious Diseases TABLES only Table V Bacteria in mice: Test methods and results (expressed as % positive results) from PritchettCorning, Cosentino, Clifford (2009),[14] and survey results from Carty 2008.[19] Agents in boldface were detected in > 1% of specimens. Gram positive bacterial agents are shaded. The final column indicates if PCR testing is commercially available for specimens from feces, oral or lung swab, or skin/fur swab. % POS Results[14] % Pos institution[19] Agent Method[14] PCR? Bordetella bronchiseptica Culture 0.00 Feces Cilia-associated respiratory bacillus Serology 0.01 Oral/lung Citrobacter rodentium Culture 0.00 Feces Culture 2 PCR 9 Skin swab Feces Corynebacterium bovis Corynebacterium kutscheri Culture 0.00 Helicobacter genus (any sp.)* PCR 16.08 - Helicobacter hepaticus PCR 12.37 Feces - Helicobacter bilis PCR 2.17 Feces Klebsiella oxytoca Culture 0.38 > 40% Feces Klebsiella pneumoniae Culture 0.10 >30% Feces Culture 0.00 Serology 0.01 PCR 0.00 Pasteurella multocida Culture 0.00 Pasteurella pneumotropica Culture 12.90 Other Pasteurella species Culture 0.31 Any Salmonella species Culture 0.00 Feces Staphylococcus aureus Culture 6.07 Feces Streptobacillus moniliformis Culture 0.00 Feces Streptococcus pneumoniae Culture 0.00 Feces Streptococcus sp. – β-haemolytic, Group B Culture 0.24 Feces Streptococcus sp. – β-haemolytic, Group G Culture 0.00 Feces Mycoplasma pulmonis cbrayton@jhmi.edu 2013 ~80% Feces <10% Feces >70% Feces Page 11 of 14 Mouse Diseases Common Conditions (phenotypes) and Infectious Diseases TABLES only Table VI: Eukaryotes: Test methods and results from Pritchett-Corning, Cosentino, Clifford (2009),[14] and survey results from Carty 2008. [19] The most common agents are in boldface. The final column indicates if PCR testing is available for specimens from feces, oral or lung swab, or skin/fur swab. Agent Fungi Encephalitozoon cuniculi Pneumocystis spp (submissions from immunodeficient mice) Enteric Protozoa Chilomastix sp. Entamoeba sp. Giardia sp. Hexamastix sp. Monocercomonoides sp. Retortamonas sp. Spironucleus sp. Trichomonads Metazoa – enteric Oxyurids (pinworms) Aspiculuris tetraptera Syphacia muris Syphacia obvelata Metazoa – Surface, external Lice Fur Mites Method[14] %Pos Results [14] Serology 0.00 PCR 1 %Pos institutions[19] PCR? Oral/ lung Not evaluated Wet mount Wet mount Wet mount Wet mount Wet mount Wet mount Wet mount Wet mount 3.74 8.08 0.00 4.45 0.04 0.03 0.08 8.88 Feces Feces >70% Direct Direct Direct 0.19 0.25 0.11 Direct Direct 0.00 0.12 Feces Feces Feces ~40% Fur swab Table VIa protozoa in mice by type and by site of infection Flagellates Coccidia Other Stomach Cryptosporidium muris Duodenum Giardia sp. Spironucleus sp. Large Intestine Chilomastix sp. Hexamastix sp. Monocercomonoides sp. Retortamonas sp. Trichomonads T muris, T diminuta etc cbrayton@jhmi.edu 2013 Jejunum Eimeria spp. Ileum Cryptosporidium parvum Large Intestine Entamoeba muris Kidney Klossiella muris Muscle Sarcocystis muris Various tissues Toxoplasma gondii Kidney / Brain [E cuniculi – now a fungus] Page 12 of 14 Mouse Diseases Common Conditions (phenotypes) and Infectious Diseases TABLES only Table VIb Features of common fur mites (oversimplified) [20] Elongate body with bulges between the legs 1st pair of legs (tarsi) are specialized for hair clasping; 2nd pair of legs has single empodial claw 300-500u long Elongate body with bulges between the legs 1st pair of legs (tarsi) are specialized for hair clasping; 2nd pair of legs has 2 unequal claws Rounded-oval T romboutsi (formerly M romboutsi) Rounded-oval 3rd and 4th pairs of legs (tarsi) are short thick and specialized for hair clasping 3rd and 4th pairs of legs (tarsi) are short thick and specialized for hair clasping 300-500u long Oval up to 250u long Base of hair shaft Feeds on interstitial fluids Deep among hairs especially of dorsal head neck shoulders flank Probably similar to M musculi Probably similar to M musculi Females oval 130x 350u Males rounded < 200u diameter Oval up to 450u long Distal hair shaft Feeds on superficial keratin layer Among hairs especially of inguinal skin and ventrum Females oval < 300u long Males rounded < 200u diameter Probably similar to M musculinus Probably similar to M musculinus R affinis (formerly M affinis) M. musculi Body shape Distinguishing features Adult size Eggs Diet Site on mouse M. musculinus TABLE VIc Comparison of features of Syphacia obvelata and Aspiculuris tetraptera [20] [21] [22] Prepatent period (egg to egg) Infectious form Larvae hatch from eggs Adult Size Aspiculuris tetraptera 21-25 days Syphacia obvelata 11–15 days S muris 7-8 days Embryonated eggs Cecum 2-4mm long, < 200u wide Embryonated eggs Cecum 1-6mm long, (males are shorter) < 400u wide Cecum lumen; females transit colon to deposit eggs at anus 350 per female all at once Not embryonated; On perineum; Embryonate within 24hr ~36u wide`, 134u long; crescentic, flattened on 1 side, pointed ends ~ S obvelata ~ S obvelata 1-4mm long, (males are shorter) < 200u wide ~ S obvelata but eggs deposited after noon all at once in afternoon Not embryonated; On perineum; Embryonate within few hours ~30u wide, 75u long; flattened on 1 side Adult location Colon lumen # eggs 17 per female per day, intermittently Not embryonated Shed in feces; Embryonate in 5-8days ~40u wide, 90u long; symmetric, Unembryonated in fresh feces Eggs cbrayton@jhmi.edu 2013 Page 13 of 14 Mouse Diseases Common Conditions (phenotypes) and Infectious Diseases TABLES only WEB RESOURCES 1. Frith, C. H. and Ward, J. M. A Color Atlas of Neoplastic and Non Neoplastic Lesions in Aging Mice. 1988. http://www.informatics.jax.org/frithbook/ also print on Demand from CL Davis Foundation http://store.cldavis.org/ 2. IMSR - FIND MICE AND ES CELL LINES http://www.findmice.org/index.jsp 3. Mouse (rat) and Gene NOMENCLATURE & apply for a laboratory code http://www.findmice.org/index.jsp 4. Mouse Phenome database - mouse data and protocols http://phenome.jax.org/ 5. Mouse Tumor Biology (MTB) Database & tumor frequency grid http://www.informatics.jax.org/mtbwi/index.do 6. Pathbase: European mutant mouse pathology database http://www.pathbase.net/ 7. RENI Tissue trimming guide http://reni.item.fraunhofer.de/reni/trimming/index.php 8. Treuting’s virtual / digital slides corresponding to Treuting & Dintzis 2012. http://repository.aperio.com/c/201/2/ REFERENCES 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16. 17. 18. 19. 20. 21. 22. Danneman, P., M. Suckow, and C. Brayton, THE LABORATORY MOUSE. 2 ed2012, Boca Raton, FL: Taylor and Francis, CRC Press. Brayton, C.F., P.M. Treuting, and J.M. Ward, Pathobiology of Aging Mice and GEM: Background Strains and Experimental Design. Veterinary pathology, 2012. 49(1): p. 85-105. Brayton, C. and P. Treuting, Phenotyping, in Comparative Anatomy and Histology: A Mouse and Human Atlas P. Treuting and S. Dintzis, Editors. 2012, Elsevier (Academic Press): London. p. 361-381. Brayton, C., Nature and Nurture: impacts on mouse phenotypes and translational research, in THE MOUSE AS A MODEL ORGANISM, T. Philajaniemi and C. Brakebusch, Editors. 2011, Springer. Festing, M.F.W. Inbred strains: Index of Major Mouse Strains. 1998 April 9, 1998 [cited 2012 July 6, 2012]; Available from: http://www.informatics.jax.org/external/festing/mouse/STRAINS.shtml. Sher, R.B., et al., Rhabdomyosarcomas in aging a/j mice. PLoS One, 2011. 6(8): p. e23498. Sellers, R., The Gene or not the Gene: That is the Question Understanding the Genetically Engineered Mouse Phenotype Vet Pathol, 2012 49(1): p. in Press Schenkel, A.R., L.C. Kingry, and R.A. Slayden, The ly49 gene family. A brief guide to the nomenclature, genetics, and role in intracellular infection. Frontiers in immunology, 2013. 4: p. 90. Vanlaere, I., et al., Mx1 causes resistance against influenza A viruses in the Mus spretus-derived inbred mouse strain SPRET/Ei. Cytokine, 2008. 42(1): p. 62-70. Staeheli, P., et al., Influenza virus-susceptible mice carry Mx genes with a large deletion or a nonsense mutation. Mol Cell Biol, 1988. 8(10): p. 4518-23. Sastalla, I., et al., Transcriptional analysis of the three Nlrp1 paralogs in mice. BMC genomics, 2013. 14: p. 188. Bradley, D.J., Letter: Genetic control of natural resistance to Leishmania donovani. Nature, 1974. 250(464): p. 353-4. JAX Choosing an Immunodeficient Mouse Model. JAXNOTES, 2006. Pritchett-Corning, K.R., J. Cosentino, and C.B. Clifford, Contemporary prevalence of infectious agents in laboratory mice and rats. Lab Anim, 2009. 43(2): p. 165-173. Mahler, M. and W. Kohl, A serological survey to evaluate contemporary prevalence of viral agents and Mycoplasma pulmonis in laboratory mice and rats in western Europe. Lab Anim (NY), 2009. 38(5): p. 161-5. Liang, C.T., et al., Microbial contaminations of laboratory mice and rats in taiwan from 2004 to 2007. J Am Assoc Lab Anim Sci, 2009. 48(4): p. 381-6. Khan, I.H., et al., Simultaneous serodetection of 10 highly prevalent mouse infectious pathogens in a single reaction by multiplex analysis. Clin Diagn Lab Immunol, 2005. 12(4): p. 513-9. Baker, D.G., Natural Pathogens of Laboratory Mice, Rats, and Rabbits and Their Effects on Research. Clin. Microbiol. Rev., 1998. 11(2): p. 231-266. Carty, A.J., Opportunistic infections of mice and rats: Jacoby and Lindsey revisited. ILAR J, 2008. 49(3): p. 272-6. Baker, D.G., Flynn’s Parasites of Laboratory Animals. 2nd ed. ACLAM, Blackwell Publishing., ed. D.G. Baker2007: ACLAM, Blackwell Publishing. Taffs, L.F., Pinworm infections in laboratory rodents: a review. Lab Anim, 1976. 10(1): p. 1-13. Clifford, C.B. and J. Watson, Old enemies, still with us after all these years. ILAR journal / National Research Council, Institute of Laboratory Animal Resources, 2008. 49(3): p. 291-302. cbrayton@jhmi.edu 2013 Page 14 of 14