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。
Study design
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。
Outcome measures
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。
Experimental animals
- Sex
- Mixed
- Tissue
- FFPE mouse kidney
Experimental procedures
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.
Model identity
- Model name
- streptozotocin-induced diabetic eNOS (Nos3) knockout mouse
- Species
- mouse
- Genetic background
- C57BL/6 (B6, as reported by the cited reviews)
- Genotype / zygosity
- eNOS (Nos3) knockout; diabetic by low-dose streptozotocin
- Modification locus
- Nos3
- Allele
- Nos3 targeted deletion
Biological characteristics
- Phenotype stage
- STZ 后数月渐进(综述汇总 AMDCC 纵向观察)。
- Research questions
- 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)。
- Limitations
- 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。
Experimental methods
Experimental protocols
- FFPE 肾组织 PAS 染色
This protocol adopts the FFPE branch of the protocols.io PAS staining protocol for human kidney tissue v3. Paraffin sections are dewaxed in xylene, rehydrated through graded alcohols, oxidized with periodic acid, stained with Schiff reagent, counterstained with hematoxylin, dehydrated, cleared and coverslipped to demonstrate glomerular basement membranes, mesangial matrix and glycoproteins. The record describes the staining procedure, not executed disease-model results.
Reagents and materials
- 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
References
- 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 guidelines