品系特点
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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.

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

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
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
等位基因参考文献
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
外观
被毛颜色
详情

 

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Related Genotype:A/A

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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