streptozotocin-induced diabetic eNOS (Nos3) knockout mouse
低剂量 STZ 糖尿病的 eNOS 缺失小鼠出现系膜扩张、系膜溶解、局灶与节段硬化、肾小球硬化渐进加重及小管间质损伤;综述将 eNOS 缺失列为加速 DKD 的机制组分。
研究设计
FFPE 肾组织切片的 PAS 染色流程,按源方案 FFPE 分支执行脱蜡、复水、氧化、Schiff 显色、苏木素复染、脱水透明和封片。具体切片厚度、视野与定量方法按研究设计确定。
结局指标
肾小球基底膜、系膜基质和糖蛋白呈 PAS 阳性(品红/紫红色),细胞核呈蓝色;按研究设计进行肾小球系膜扩张或病变范围判读。
实验动物
- 性别
- 混合
- 组织
- FFPE mouse kidney
实验步骤
Start with FFPE here: Allow PAS “kit” to come to room temperature on the bench. Start with FFPE here: For paraffin sections, deparaffinize in xylene, two changes, 00:03:00 each. Start with FFPE here: Hydrate through graded alcohols, 00:01:00 each: 100%, 100%, 95%, 70%, water Start with FFPE here: Rinse well in distilled water by holding finger over slides, pouring water into sink and adding water. Do this 5 times. Start Frozen samples here: Place in 0.5% Periodic acid for 00:10:00 (to oxidize). Start Frozen samples here: Rinse well in distilled water (follow Step 4). Start Frozen samples here: Pour Schiff’s reagent into Coplin jar containing slides. Allow to sit 15-30 minutes at room temperature (kidney samples ~30 minutes). Start Frozen samples here: Rinse in running warm (~40 °C) distilled or tap water (follow Step 4). The tissue should appear pink after rinsing with warm water. Start Frozen samples here: Place slides in movable gray slide holder. Start Frozen samples here: Counterstain in Hematoxylin (staining line) for 00:01:00. Start Frozen samples here: Rinse well in distilled water, starting with blue container next to hematoxylin (follow Step 4). Start Frozen samples here: Quickly dip slides into “Bluing” agent (0.5% ammonium hydroxide). Start Frozen samples here: Rinse 1 minute in distilled water until pink color is visible (follow Step 4). Start Frozen samples here: Dehydrate through graded alcohols, 10 short dips in each: 95%, 95%, 100%, 100% If the last 100% ethanol rinse is colored by residual stain, additional washing in new 100% ethanol solution should be performed. Start Frozen samples here: Fix in 2 rounds of xylenes, 00:01:00 each (in the hood). Start Frozen samples here: Coverslip slides: - Place coverslip on paper towel - Add 2-3 drops of cytoseal to edge (depending on size) - Dip slide into xylenes, take out and roll the xylene lengthwise on slide - Line up slide and cover slip and slowly place the slide on the coverslip - If needed, use dissecting tool to remove bubbles Start Frozen samples here: Image slides using a Leica brightfield scanner, AxioScan Z1 slide scanner (or equivalent) at 20x (~1 µm spatial resolution) and save as.tiff or.jpg file.
模型身份
- 模型名称
- streptozotocin-induced diabetic eNOS (Nos3) knockout mouse
- 物种
- mouse
- 遗传背景
- C57BL/6 (B6, as reported by the cited reviews)
- 基因型/合子状态
- eNOS (Nos3) knockout; diabetic by low-dose streptozotocin
- 遗传修饰位点
- Nos3
- 等位基因
- Nos3 targeted deletion
生物学特性
- 表型出现阶段
- STZ 后数月渐进(综述汇总 AMDCC 纵向观察)。
- 适用研究问题
- eNOS 缺失如何放大糖尿病肾小球病变(尿白蛋白、GFR、肾组织形态学终点)。
- 模型局限
- 本包内该模型的可定位证据来自模型综述的汇总结论(含 AMDCC 数据),语料中没有以该基因型完整描述的原研全文;品系/亚系细节以原综述记载为限。
实验方法
实验方案
- FFPE 肾组织 PAS 染色
本方案采用 protocols.io 人肾组织 PAS 染色 v3 的 FFPE 分支。石蜡切片经二甲苯脱蜡、梯度乙醇复水后,以高碘酸氧化、Schiff 试剂显色、苏木素复染,脱水透明并封片;用于显示肾小球基底膜、系膜基质及糖蛋白类物质。方案描述染色安排,不包含具体疾病模型的实验结果。
配套试剂与材料
- Cytoseal 封片剂
封片
- Ethanol
梯度复水
- 组织学二甲苯(混合异构体)
脱蜡
- 苏木素染液
细胞核复染
- PAS 染色试剂盒(黏液染色,Abcam ab150680)
高碘酸氧化与 PAS 染色
参考文献
- Mouse models of diabetic nephropathy (AMDCC review of B6-eNOS-/- low-dose STZ phenotype) (PMID 19729434)
- Animal Models of Kidney Disease: Challenges and Perspectives (STZ in eNOS-deficient mice row) (PMID 37526653)
- Elizabeth Neumann, Jamie Allen, Angela R.S. Kruse, Jennifer Harvey, Maya Brewer, Carrie Romer, Mark De Caestecker, Jeff Spraggins. PAS Staining of Fresh Frozen or Paraffin Embedded Human Kidney Tissue. protocols.io v3, 2023. https://doi.org/10.17504/protocols.io.x54v98nkzl3e/v3
- ARRIVE 2.0 官方规范