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C3H/HeJ
品系货号:000659 | 通用名称:C3H
又名:C3H Heston 小鼠、C3 小鼠、C3H 小鼠
C3H/HeJ 小鼠通常称为 C3H 小鼠,作为一种常规品系广泛用于多种研究领域,包括癌症、传染病、感觉神经和心血管生物学研究。C3H/HeJ 品系的脂多糖应答位点上发生Tlr4 自发突变(toll 样受体 4 基因突变,Tlr4Lps-d),使C3H/HeJ小鼠对内毒素具有更高的耐受性。C3H/HeJ小鼠对革兰氏阴性菌(如肠沙门氏菌)高度易感。杰克森实验室提供的C3H亚系为视网膜变性1基因 (Pde6brd1) 突变的纯合小鼠,该突变会造成小鼠在离乳期失明。
重点提示:此品系小鼠不携带小鼠乳腺肿瘤病毒 (mouse mammary tumor virus, MMTV)。本品系为视网膜退化等位基因 Pde6brd1 纯合子,脂多糖应答等位基因缺陷 Tlr4Lps-d纯合子,6 号染色体倒位纯合子。视力正常的替代小鼠品系货号为 003648,C3Sn.BLiA-Pde6b+/DnJ。
品系特点
原始参考文献
Info 当使用该小鼠品系发表文献时,请引用原始文献,并在材料方法中提供该品系的品系货号:JAX stock#000659
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品系详情
C3H/HeJ 小鼠作为一种常规品系广泛用于多种研究领域,包括癌症、免疫性炎症、感觉神经和心血管生物学研究。C3H/HeJ 小鼠和杰克森实验室提供的其他亚系均为视网膜变性 1 基因 (Pde6brd1) 突变的纯合小鼠,该突变会造成小鼠在离乳期失明,但不含 Gpr179 的 nob5 等位基因 (Chang, 2015)。C3H/HeJ 小鼠常见腹部白斑,表型范围从少许白毛至明显白斑不等。同时,C3H 小鼠的肝癌发病率也较高(有报告称,14 月龄雄性、未经交配的雌性和繁育期雌性小鼠的发病率分别为 72-91%、59% 和 30-38%)。尽管无外源性小鼠乳腺肿瘤病毒 (exogenous mouse mammary tumor virus, MMTV),但未经交配的雌性和繁育期雌鼠年长后仍有可能出现乳腺肿瘤。与几种高度易感品系小鼠不同(如 C57BL/6J,品系货号 000664;C57L/J,品系货号 000668;C57BR/cdJ,品系货号 000667 和 SM/J,品系货号 000687),C3H/HeJ 小鼠喂食致动脉硬化饲料(1.25% 胆固醇、0.5% 胆酸和 15% 脂肪)后未出现动脉粥样硬化主动脉病变。C3H/HeJ 小鼠会自发出现斑秃 (alopecia areata, AA),到 5 月龄时报告的发病率约 0.25%。 据报道,老龄小鼠(12-18 月龄)中斑秃的发病率可接近 20%。雌鼠在 3-5 月龄时就有可能出现 AA,而雄鼠发病时间通常延至 6 月龄之后。斑秃可通过手术诱导形成,方法是从患有 AA 的老年供体动物取小片皮肤移植到同背景C3H/HeJ 受体年轻动物上。

C3H/HeJ 品系的脂多糖应答位点发生自发突变(后续鉴定为 toll 样受体 4 基因突变,Tlr4Lps-d),使 C3H/HeJ 小鼠对内毒素具有更高的耐受性。C3H/HeJ 小鼠 (Tlr4Lps-d) 对革兰氏阴性菌(如肠沙门氏菌)高度易感。感染沙门氏菌的小鼠表现为趋化因子产生延迟,一氧化氮生成障碍以及细胞免疫应答减弱。 感染小鼠的死亡原因可能是因为 Kupffer 细胞网状结构被大量增殖的细菌所破坏 (Vazquez-Torres et al., 2004)。C3H/HeJ 亚系是 6 号染色体反转倒位的纯合小鼠(符号:In(6)1J)。6 号染色体上 D6Mit124(约 30.3 cM)和 D6Mit150(约 51.0 cM)之间有 20% 的长度发生反转倒位,但未报告表型。筛选其他 C3H 亚系和 C3H/HeJ 冷冻保存品系的结果表明,该突变的发生时间在 1952 年以后。C3H/HeJ 品系存在棘波放电 1(Gria4spkw1) 自发突变,而 C3HeB/FeJ 品系不存在这种突变。此突变的纯合小鼠有中等失神癫痫发病率。此品系也是 Pcnx2 亚等位基因纯合小鼠,该等位基因通过 IAP 插入获得,降低了 Gria4spkw1 所致失神癫痫发作表型的严重程度 (Frankel et al., 2014)。
品系建立
1920 年,LC Strong 用 Bagg 白化雌鼠与 DBA 雄鼠杂交,然后选择乳腺肿瘤发病率高的后代,建立了 C3H 亲本品系 (L.C.Strong, 1935)。其发病率高的原因是外源性小鼠乳腺肿瘤病毒 (mouse mammary tumor virus, MMTV) 经母乳传播。杰克森实验室目前保留有四种无外源性 MMTV 的 C3H 亚系,即 C3H/HeJ(品系货号 000659)、C3H/HeOuJ(品系货号 000635)、C3HeB/FeJ(品系货号 000658)和 C3H/HeSnJ(品系货号 000661)。C3H/HeJ 和 C3H/HeOuJ 小鼠以前携带 MMTV,但在 1999 年,为提高小鼠的整体健康状况,重新净化了这两个品系,但未重新引入该病毒。C3H/HeJ 和 C3H/HeOuJ 亚系于 1952 年分离得到,二者在遗传组成上非常相似。不过,C3H/HeJ 品系小鼠于 1960 年至 1968 年期间发生脂多糖应答位点自发突变(toll 样受体 4 基因突变,Tlr4Lps),使 C3H/HeJ 小鼠对内毒素具有耐受性,而其他三种 C3H 品系小鼠对内毒素易感。
参考文献
精选参考文献
当使用该小鼠品系发表文献时,请引用原始文献,并在材料方法中提供该品系的品系货号:JAX stock#000659
2015

Survey of the nob5 mutation in C3H substrains.

Chang B , et al.

PubMed:26396487

MGI:J:224435

Mol Vis 21:1101-5

2014

Unraveling genetic modifiers in the gria4 mouse model of absence epilepsy.

Frankel WN , et al.

PubMed:25010494

MGI:J:228536

PLoS Genet 10(7):e1004454

2006

Chromosomal inversion discovered in C3H/HeJ mice.

FAkeson EC , et al.

PubMed:16309882

MGI:J:105810

Genomics 87(2):311-3

基因分型和繁育
Allele Symbol Tlr4<Lps-d>
Allele Specific Protocols
  
此品系繁育表现良好。
繁育策略
同胞兄弟姐妹交配
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000659
C3H
肿瘤、传染病、感觉神经、心血管生物学研究、斑秃
参考文献|
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    精选参考文献
    当使用该小鼠品系发表文献时,请引用原始文献,并在材料方法中提供该品系的品系货号:JAX stock#000659

    2015
    Survey of the nob5 mutation in C3H substrains.
    Chang B , et al.
    PubMed:26396487
    MGI:J:224435
    Mol Vis 21:1101-5

    2014
    Unraveling genetic modifiers in the gria4 mouse model of absence epilepsy.
    Frankel WN , et al.
    PubMed:25010494
    MGI:J:228536
    PLoS Genet 10(7):e1004454

    2006
    Chromosomal inversion discovered in C3H/HeJ mice.
    Akeson EC , et al.
    PubMed:16309882
    MGI:J:105810
    Genomics 87(2):311-3

    2004
    Development of a SNP genotyping panel for genetic monitoring of the laboratory mouse.
    Petkov PM , et al.
    PubMed:15081119
    MGI:J:89298
    Genomics 83(5):902-11

    1995
    Genetics of liver tumor susceptibility in mice.
    Dragani TA , et al.
    PubMed:8597117
    MGI:J:31816
    Toxicol Lett 82-3:613-619

    1985
    Attenuation of exogenous murine mammary tumor virus virulence in the C3H/HeJ mouse substrain bearing the Lps mutation.
    Outzen HC , et al.
    PubMed:2997536
    MGI:J:24864
    J Natl Cancer Inst 75(5):917-23

    1978
    Resistance and susceptibility of mice to bacterial infection: genetics of listeriosis.
    Cheers C , et al.
    PubMed:305895
    MGI:J:5965
    Infect Immun 19(3):755-62

    1971
    Mammary tumors, plaques, and hyperplastic alveolar nodules in various combinations of mouse inbred strains and the different lines of the mammary tumor virus.
    Heston WE , et al.
    PubMed:4322934
    MGI:J:24674
    Int J Cancer 7(1):141-8

    1935
    The Establishment of the C(3)H Inbred Strain of Mice for the Study of Spontaneous Carcinoma of the Mammary Gland.
    Strong LC , et al.
    PubMed:17246779
    MGI:J:2480
    Genetics 20(6):586-91

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    其他参考文献

    2011
    Mouse genomic variation and its effect on phenotypes and gene regulation.
    Keane TM , et al.
    PubMed:21921910
    MGI:J:177037
    Nature 477(7364):289-94

    2007
    Mouse behavioral tasks relevant to autism: phenotypes of 10 inbred strains.
    Moy SS , et al.
    PubMed:16971002
    MGI:J:138682
    Behav Brain Res 176(1):4-20

    2007
    Substance P as an immunomodulatory neuropeptide in a mouse model for autoimmune hair loss (alopecia areata).
    Siebenhaar F , et al.
    PubMed:17273166
    MGI:J:122923
    J Invest Dermatol 127(6):1489-97

    2004
    Genetic analysis of blood pressure in C3H/HeJ and SWR/J mice.
    DiPetrillo K , et al.
    PubMed:14996992
    MGI:J:89267
    Physiol Genomics 17(2):215-20

    2004
    Strain distribution pattern of susceptibility to immune-mediated nephritis.
    Xie C , et al.
    PubMed:15067087
    MGI:J:122988
    J Immunol 172(8):5047-55

    2003
    Major locus on mouse chromosome 17 and minor locus on chromosome 9 are linked with alopecia areata in C3H/HeJ mice.
    Sundberg JP , et al.
    PubMed:12713579
    MGI:J:83350
    J Invest Dermatol 120(5):771-5

    2000
    Quantitative trait loci controlling allergen-induced airway hyperresponsiveness in inbred mice.
    Ewart SL , et al.
    PubMed:11017920
    MGI:J:66641
    Am J Respir Cell Mol Biol 23(4):537-45

    1999
    Spontaneous alopecia areata-like hair loss in one congenic and seven inbred laboratory mouse strains
    McElwee KJ , et al.
    PubMed:10674366
    MGI:J:60482
    J Investig Dermatol Symp Proc 4(3):202-6

    1998
    Experimental induction of alopecia areata-like hair loss in C3H/HeJ mice using full-thickness skin grafts.
    McElwee KJ , et al.
    PubMed:9804341
    MGI:J:111520
    J Invest Dermatol 111(5):797-803

    1998
    Ltx1, a mouse locus that influences the susceptibility of macrophages to cytolysis caused by intoxication with Bacillus anthracis lethal factor, maps to chromosome 11.
    Roberts JE , et al.
    PubMed:9720874
    MGI:J:49726
    Mol Microbiol 29(2):581-91

    1994
    Alopecia areata in aging C3H/HeJ mice.
    Sundberg JP , et al.
    PubMed:8006447
    MGI:J:18877
    J Invest Dermatol 102(6):847-56

    1992
    Dietary obesity in nine inbred mouse strains.
    West DB , et al.
    PubMed:1621856
    MGI:J:1348
    Am J Physiol 262(6 Pt 2):R1025-32

    1991
    Live vaccine strain of Francisella tularensis: infection and immunity in mice.
    Fortier AH , et al.
    PubMed:1879918
    MGI:J:27016
    Infect Immun 59(9):2922-8

    1990
    Atherosclerosis susceptibility differences among progenitors of recombinant inbred strains of mice.
    Paigen B , et al.
    PubMed:2317166
    MGI:J:22615
    Arteriosclerosis 10(2):316-23

    1986
    Differences in susceptibility of inbred mice to Bacillus anthracis.
    Welkos SL , et al.
    PubMed:3081444
    MGI:J:8197
    Infect Immun 51(3):795-800

    1983
    Genetics of beta-2 microglobulin in the mouse.
    Michaelson J , et al.
    PubMed:6187676
    MGI:J:7014
    Immunogenetics 17(3):219-60

    1978
    The inflammatory response and resistance to endotoxin in mice.
    Moeller GR , et al.
    PubMed:627714
    MGI:J:5936
    J Immunol 120(1):116-23

    1972
    Genetic relationships between inbred strains of mice.
    Taylor BA , et al.
    PubMed:5031317
    MGI:J:24288
    J Hered 63(2):83-6

    1968
    Genetic control of leucocyte responses to endotoxin.
    Sultzer BM , et al.
    PubMed:4877918
    MGI:J:5087
    Nature 219(160):1253-4

    1952
    COMMITTEE on Standardized Nomenclature for Inbred Strains of Mice
    International Nomenclature Committee , et al.
    PubMed:14945054
    MGI:J:166288
    Cancer Res 12(8):602-13

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