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BKS.Cg-Dock7m +/+ Leprdb/J
品系货号:000642
又名:BKS db
摘要
该品系用于肥胖症和 II 型糖尿病的 I 至 III 期建模。糖尿病自发突变 (Leprdb) 纯合的小鼠表现为病态肥胖、慢性高血糖症、胰岛 β 细胞萎缩和低胰岛素血症。小鼠在约 3 至 4 周龄时表现出肥胖症。血浆胰岛素升高开始于 10 至 14 日龄,血糖升高开始于 4 至 8 周龄。纯合突变小鼠表现为多食、烦渴和多尿。BKS遗传背景下的疾病严重程度可导致不可控的血糖上升,胰岛生产胰岛素的beta细胞严重耗竭,周围神经病变,心肌疾病,10月龄时死亡。外源性胰岛素无法控制血糖水平,糖异生酶活性增加。伤口愈合延迟,代谢效率提高。
重要提示:该品系保持Dock7mLeprdb互斥。尽管两个基因紧密连锁,但仍有极小的可能发生重组。我们提供的杂合小鼠被认为是非重组的,但是并未经过验证。
品系特点
同源品系
 
  
自发突变
 
  
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 #000642
查阅参考文献 >
品系详情

糖尿病自发突变 (Leprdb) 纯合的小鼠在约 3 至 4 周龄时肥胖明显。血浆胰岛素升高开始于 10 至 14 日龄,血糖升高开始于 4 至 8 周龄。纯合突变小鼠表现为多食、烦渴和多尿。病程受遗传背景影响显著。在 C57BLKS 遗传背景下观察到许多特征,包括血糖不受控制的升高、胰岛中产胰岛素的 β 细胞严重耗竭以及 10 月龄前死亡。外源胰岛素无法控制血糖水平,糖异生酶活性升高。在 C57BLKS-Leprdb 纯合子中观察到周围神经病变和心肌疾病。伤口愈合延迟,代谢效率提高。纯合雌鼠表现出子宫和卵巢重量降低、卵巢激素产生减少以及卵泡粒细胞和子宫内膜上皮组织层中的高细胞脂血症 (Garris et al., 2004)。

 

尽管杂合子小鼠 (Leprdb/+) 具有正常的体重,血糖和血浆胰岛素水平,但其代谢效率也有所提高,在长时间禁食处理时,与对照组相比,可以存活更长的时间。涉及破坏下丘脑腹内侧核的实验表明,Leprdb 突变可能导致下丘脑功能缺陷。在糖尿病小鼠中异常表达的类固醇磺基转移酶与 Leprdb突变相互作用,作为肥胖诱导的糖尿病易感性性别差异的修饰因子。由于 Leprdb 纯合子是不育的,因此 misty (Dock7m) 突变已被整合到品系中,用于维持糖尿病突变。互斥双重杂合子 (Dock7m +/+ Leprdb) 用于识别育种用的杂合子,而偶联双重杂合子 (Dock7m Leprdb/+ +) 可在严重表型出现前识别纯合子。

 

隐性的 misty 突变会导致轻微的小鼠被毛毛色变浅,在某些遗传背景下可见尾尖呈白色,并伴有腹部斑点。Dock7m/Dock7m 小鼠的黑素细胞呈现高度树突状,在培养中表现出增殖缺陷,且黑色素含量更多。在 Dock7m/Dock7m 小鼠的原代培养物中发现的黑素母细胞少于野生型对照组。在 2 至 5 周龄,Dock7m/Dock7m 小鼠的体形小于对照组。与对照相比,35 日龄时,它们体长较短,体重平均轻 15%,腹股沟脂肪量也较少。Misty 纯合子完全没有棕色脂肪。虽然 Dock7m/Dock7m 纯合子血小板计数、褪黑素含量和 ATP 含量正常,但它们的凝血时间延长(出血时间延长)且血小板 ADP 水平降低。(Woolley 1941 and 1945; Truett et al.1998; Sviderskaya et al.1998.)

品系建立
1966年,杰克森实验室(缅因州巴港)首次在近交系C57BLKS/J (BKS)上发现自发性常染色体隐性突变糖尿病(db)。随后该品系与携带毛色基因misty (m)的BKS品系杂交,该基因与位于小鼠4号染色体上的Lepr位点紧密连锁。该品系中Dock7mLeprdb保持互斥。
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 #000642。
2001

Leptin and puberty: a review.

Gueorguiev M , et al.

 

PubMed:11824512

MGI:J:109856

Pituitary 4(1-2):79-86

2000

Leptin in the regulation of immunity, inflammation, and hematopoiesis.

Fantuzzi G , et al.

 

PubMed:11037963

MGI:J:109886

J Leukoc Biol 68(4):437-46

2000

Lack of interferon-gamma production despite the presence of interleukin-18 during cutaneous wound healing.

Kampfer H , et al.

 

PubMed:11474118

MGI:J:109870

Mol Med 6(12):1016-27

基因分型和繁育
Dock7m +/+ < ... Dock7m +/+ Leprdb (Heterozygote from the colony)
                                                           
Dock7m +/ ... Dock7m +/Dock7m + from the colony

C57BLKS/J

Allele Symbol Dock7<m>
Allele Specific Protocols
Allele Symbol Dock7<m> qPCR
Allele Specific Protocols
Allele Symbol Dock7<m>-Probe
Allele Specific Protocols
Allele Symbol Lepr<db>
Allele Specific Protocols

由于 Leprdb 纯合雄性和雌性小鼠均不育,因此将紧密连锁的毛色突变基因 m 整合到品系中,用于维持 db 突变。通过交配双重互斥杂合子 Dock7m +/+ Leprdb 进行育种,推测有 1/4 糖尿病小鼠(黑色,断奶时肥胖)可用于研究,有 1/2 野生型双重互斥杂合子小鼠(黑色,较瘦)可用于进一步育种,有 1/4 misty 突变小鼠(灰色,较瘦)会被丢弃。Dock7mLeprdb 基因座的重组风险仅约 2%,满 3 日龄幼鼠如果爪部和尾尖无色素沉着,即可认为存在风险。饮食限制能够延长寿命,食用无碳水化合物、富含蛋白质的特定饲料可明显降低疾病严重程度。

离乳小鼠可能表现出包括掉须在内的理毛现象。受影响小鼠通常在离乳后两周内重新长出胡须。

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000642
BKS db
000642
肥胖症,糖尿病
参考文献|
x
  •  
    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 #000642

    2001
    Leptin and puberty: a review.
    Gueorguiev M , et al.
    PubMed:11824512
    MGI:J:109856
    Pituitary 4(1-2):79-86

    2000
    Leptin in the regulation of immunity, inflammation, and hematopoiesis.
    Fantuzzi G , et al.
    PubMed:11037963
    MGI:J:109886
    J Leukoc Biol 68(4):437-46

    2000
    Lack of interferon-gamma production despite the presence of interleukin-18 during cutaneous wound healing.
    Kampfer H , et al.
    PubMed:11474118
    MGI:J:109870
    Mol Med 6(12):1016-27

    1996
    Evidence that the diabetes gene encodes the leptin receptor: identification of a mutation in the leptin receptor gene in db/db mice.
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    Cell 84(3):491-5

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    MGI:J:31419
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    1996
    Abnormal splicing of the leptin receptor in diabetic mice.
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    MGI:J:31327
    Nature 379(6566):632-5

    1994
    Obesity-induced diabetes (diabesity) in C57BL/KsJ mice produces aberrant trans-regulation of sex steroid sulfotransferase genes.
    Leiter EH , et al.
    PubMed:8182132
    MGI:J:17991
    J Clin Invest 93(5):2007-13

    1988
    Molecular mimicry between insulin and retroviral antigen p73. Development of cross-reactive autoantibodies in sera of NOD and C57BL/KsJ db/db mice.
    Serreze DV , et al.
    PubMed:3286334
    MGI:J:27625
    Diabetes 37(3):351-8

    1988
    Genetic control of organ-reactive autoantibody production in mice by obesity (ob) diabetes (db) genes.
    Yoon JW , et al.
    PubMed:3044893
    MGI:J:109940
    Diabetes 37(9):1287-93

    1984
    Autoimmune mice develop antibodies to thymic hormone: production of anti-thymulin monoclonal autoantibodies from diabetic (db/db) and B/W mice.
    Dardenne M , et al.
    PubMed:6539799
    MGI:J:109953
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    1978
    Impairment of cell-mediated immunity in mutation diabetic mice (db/db).
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    PubMed:347001
    MGI:J:109964
    J Immunol 120(4):1375-7

    1966
    Diabetes, a new mutation in the mouse.
    Hummel KP , et al.
    PubMed:5918576
    MGI:J:5010
    Science 153(740):1127-8

  •  
    其他参考文献


    2004
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    He H , et al.
    PubMed:14525917
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    2004
    Development of a SNP genotyping panel for genetic monitoring of the laboratory mouse.
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    PubMed:15081119
    MGI:J:89298
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    2004
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    2003
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    PubMed:14578300
    MGI:J:86304
    Diabetes 52(11):2805-13

    2003
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    2003
    Altering dietary protein type and quantity reduces urinary albumin excretion without affecting plasma glucose concentrations in BKS.cg-m +Lepr db/+Lepr db (db/db) mice.
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    PubMed:12612136
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    2003
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    2003
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    Wendt TM , et al.
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    2002
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    PubMed:12091495
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    2002
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    2002
    Altered red cell turnover in diabetic mice.
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    PubMed:12271273
    MGI:J:79265
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    2002
    Echocardiographic assessment of cardiac function in diabetic db/db and transgenic db/db-hGLUT4 mice.
    Semeniuk LM , et al.
    PubMed:12181126
    MGI:J:78898
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    2002
    Phosphatidylinositol 3-kinase redistribution is associated with skeletal muscle insulin resistance in gestational diabetes mellitus.
    Shao J , et al.
    PubMed:11756318
    MGI:J:73759
    Diabetes 51(1):19-29

    2001
    Leptin-regulated endocannabinoids are involved in maintaining food intake.
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    2001
    Platelet-derived Growth Factor C (PDGF-C), a Novel Growth Factor That Binds to PDGF alpha and beta Receptor.
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    2001
    Metabolic responses to leptin in obese db/db mice are strain dependent.
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    2001
    Increased glomerular and tubular expression of transforming growth factor-beta1, its type II receptor, and activation of the Smad signaling pathway in the db/db mouse.
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    PubMed:11337363
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    2000
    Leptin as a modulator of sweet taste sensitivities in mice
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    Proc Natl Acad Sci U S A 97(20):11044-9

    2000
    Up-regulation of peroxisome proliferator-activated receptors (PPAR-alpha) and PPAR-gamma messenger ribonucleic acid expression in the liver in murine obesity: troglitazone induces expression of PPAR-gamma-responsive adipose tissue-specific genes in the liver of obese diabetic mice [In Process Citation]
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    1998
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    1998
    Misty (m) affects growth traits.
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    1996
    Researchers nail down leptin receptor [news; comment]
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    MGI:J:31488
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    1995
    Prevention of diabetic nephropathy in db/db mice with glycated albumin antagonists. A novel treatment strategy.
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    1994
    Mapping of PCR-based markers for mouse chromosome 4 on a backcross penetrant for the misty (m) mutation.
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    1994
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    1979
    Thermoregulation in the diabetic-obese (db/db) mouse. The role of non-shivering thermogenesis in energy balance.
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    1978
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    1977
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    等位基因参考文献



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外观
详情

Leprdb: black, fat

Related Genotype: a/a + Leprdb/+ Leprdb

Note: Wildtype for Dock7,

Homozygous for Leprdb

 

Dock7m Leprdb: black, lean

Related Genotype: a/a Dock7m +/+Leprdb

Note: Heterozygous for Dock7m,

Heterozygous for Leprdb

 

Dock7m: misty (grey), lean

Related Genotype: a/a Dock7m +/Dock7m +

Note: Homozygous for Dock7m,

Wildtype for Lepr