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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.)
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Gueorguiev M , et al.
Leptin in the regulation of immunity, inflammation, and hematopoiesis.
Fantuzzi G , et al.
Lack of interferon-gamma production despite the presence of interleukin-18 during cutaneous wound healing.
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C57BLKS/J
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。Dock7m 和 Leprdb 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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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
2001Leptin and puberty: a review.
Gueorguiev M , et al.
2000Leptin in the regulation of immunity, inflammation, and hematopoiesis.
Fantuzzi G , et al.
2000Lack of interferon-gamma production despite the presence of interleukin-18 during cutaneous wound healing.
Kampfer H , et al.
1996Evidence 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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Serreze DV , et al.
1988Genetic control of organ-reactive autoantibody production in mice by obesity (ob) diabetes (db) genes.
Yoon JW , et al.
1984Autoimmune mice develop antibodies to thymic hormone: production of anti-thymulin monoclonal autoantibodies from diabetic (db/db) and B/W mice.
Dardenne M , et al.
1978Impairment of cell-mediated immunity in mutation diabetic mice (db/db).
Mandel MA , et al.
1966Diabetes, a new mutation in the mouse.
Hummel KP , et al. -
其他参考文献
2004Diabetes causes decreased osteoclastogenesis, reduced bone formation, and enhanced apoptosis of osteoblastic cells in bacteria stimulated bone loss.
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Wang YX , et al.
2003RAGE Drives the Development of Glomerulosclerosis and Implicates Podocyte Activation in the Pathogenesis of Diabetic Nephropathy.
Wendt TM , et al.
2002Cholesterol gallstone formation in overweight mice establishes that obesity per se is not linked directly to cholelithiasis risk.
Bouchard G , et al.
2002Nicotine accelerates angiogenesis and wound healing in genetically diabetic mice.
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2002Altered red cell turnover in diabetic mice.
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2002Echocardiographic assessment of cardiac function in diabetic db/db and transgenic db/db-hGLUT4 mice.
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2002Phosphatidylinositol 3-kinase redistribution is associated with skeletal muscle insulin resistance in gestational diabetes mellitus.
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2001Leptin-regulated endocannabinoids are involved in maintaining food intake.
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2001Platelet-derived Growth Factor C (PDGF-C), a Novel Growth Factor That Binds to PDGF alpha and beta Receptor.
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2001Metabolic responses to leptin in obese db/db mice are strain dependent.
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2001Increased 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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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
