CDH5 Mouse

Cadherin 5 Mouse Recombinant
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Description

Genetic Design and Variants

CDH5 mouse models employ different regulatory elements and induction systems:

Model TypePromoter RegionInduction SystemKey FeaturesEarliest ActivityNon-EC ExpressionReference
Tg(Cdh5-cre)7Mlia2.2 kb promoterConstitutivePan-EC activity, sporadic early expressionE7.5Hematopoietic cells
Tg(Cdh5-cre)1Spe2.2 kb + insulatorsConstitutivePatchy embryonic expression, adult pan-ECE9.5Hematopoietic cells
Cdh5(PAC)-CreERT2PAC-derived promoterTamoxifen-inducible95%+ endothelial specificity, no baseline activityE9.5 (induced)None reported
Tg(Cdh5-cre/ERT2)CIVE23Mlia2.2 kb promoterTamoxifen-inducibleEmbryonic and adult EC targetingE9.5 (induced)Hematopoietic cells

Key technical features:

  • Inducible systems require tamoxifen administration for Cre activation

  • Constitutive models show variable penetrance during embryogenesis

  • All models demonstrate near-complete endothelial coverage in adult vasculature

Angiogenesis Studies

  • Enabled identification of circMET as critical for pathological angiogenesis through EC-specific knockdown

  • Demonstrated HIF2α regulation of CDH5 in glioblastoma stem cells under hypoxia

  • Facilitated mapping of endothelial-hematopoietic lineage relationships

Vascular Development

  • Revealed Cdh5-lineage-independent origins of dermal lymphatics

  • Characterized VE-cadherin's role in vascular integrity through conditional knockout models

Disease Modeling

Disease ModelApplicationKey FindingReference
Pulmonary hypertensionEndothelial reporter ratsIdentified microvascular EC heterogeneity
CancerGlioblastoma xenograftsLinked CDH5 overexpression to poor prognosis
RetinopathyOcular injection modelsEstablished EC-specific RNA interference methods

Specificity Challenges

  • 85-96% of hematopoietic cells show Cre activity in constitutive models

  • Tamoxifen-inducible versions reduce but don't eliminate off-target effects

  • Endothelial specificity improves with PAC-derived promoters vs traditional constructs

Protocol Optimization

  • Tamoxifen dosing (75 mg/kg for 5 days) achieves >95% EC recombination

  • Neonatal models require adjusted induction protocols

  • Background strain affects penetrance (C57BL6 > FVB/N)

Limitations and Solutions

Challenge: Hematopoietic cell recombination
Mitigation: Use inducible models with timed tamoxifen administration

Challenge: Embryonic lethality in full knockouts
Solution: Employ tissue-specific conditional alleles

Challenge: Regional expression variability
Approach: Combine with regional markers (e.g., Aplnr for venous ECs)

Recent Advancements (2022-2025)

  • Development of first CDH5-CreERT2 rat model with superior microvascular resolution

  • Optimization of single-cell RNA-seq compatibility in lineage tracing

  • Creation of dual-reporter systems for simultaneous EC/progenitor tracking

Product Specs

Introduction
Cadherin-5, also known as CDH5, is a member of the cadherin superfamily and functions as a classical cadherin. Located within a six-cadherin cluster on chromosome 16, CDH5 is implicated in the loss of heterozygosity events observed in both breast and prostate cancer. This calcium-dependent cell-cell adhesion glycoprotein is composed of five extracellular cadherin repeats, a transmembrane region, and a highly conserved cytoplasmic tail. CDH5 confers cells with the ability to adhere in a homophilic manner, playing a crucial role in endothelial cell biology by regulating the cohesion and organization of intercellular junctions.
Description

Produced in Sf9 Insect cells, CDH5 is a single, glycosylated polypeptide chain with a molecular weight of 66.2 kDa (25-599 amino acids). It appears as a band at approximately 70-100 kDa on SDS-PAGE. The protein is expressed with an 8 amino acid His tag at the C-terminus and purified using proprietary chromatographic techniques.

Physical Appearance
A clear, colorless solution that has been sterilized by filtration.
Formulation
The CDH5 protein solution is provided at a concentration of 0.5 mg/ml and contains phosphate buffered saline (pH 7.4) and 10% glycerol.
Stability
For short-term storage (up to 4 weeks), the CDH5 protein should be stored at 4°C. For extended storage, it is recommended to store the protein at -20°C. The addition of a carrier protein (0.1% HSA or BSA) is advisable for long-term storage. To maintain protein integrity, avoid repeated freeze-thaw cycles.
Purity
The purity of CDH5 is greater than 90% as determined by SDS-PAGE analysis.
Synonyms
Cadherin-5, Vascular endothelial cadherin, VE-cadherin, CD144, Cdh5.
Source

Sf9, Insect cells.

Amino Acid Sequence
GPNFPQIDTP NMLPAHHRQK RDWIWNQMHI DEEKNESLPH YVGKIKSNVN RQNAKYVLQG EFAGKIFGVD ANTGNVLAYE RLDREKVSEY FLTALIVDKN TNKNLEQPSS FTVKVHDIND NWPVFSHQVF NASVPEMSAI GTSVIRVTAV DADDPTVAGH ATVLYQIVKG NEYFSIDNSG LIFTKIKNLD REKQAEYKIV VETQDALGLR GESGTATVMI RLEDINDNFP VFTQSTYTFS VPEDIRVGKP LGFLTVVDPD EPQNRMTKYS IMQGEYRDTF TIETDPKRNE GIIKPTKSLD YEVIQQYTFY IEATDPTIRY EYLSSTSGKN KAMVTINVLD VDEPPVFQRH FYHFKLPENQ KKPLIGTVVA KDPDKAQRSI GYSIRKTSDR GQFFRITKQG NIYNEKELDR ETYAWYNLTV EANELDSRGN PVGKESIVQV YIEVLDENDN PPEFAQPYEP KVCENAAQGK LVVQISATDK DVVPVNPKFK FALKNEDSNF TLINNHDNTA NITVKYGQFN REHAKFHYLP VLISDNGVPS LTGTSTLTVG VCKCNEQGEF TFCEEMAAQA GVSIQLEHHH HHH.

Product Science Overview

Gene and Protein Structure

The Cdh5 gene is located on chromosome 8 in mice and spans approximately 42.9 kb. It consists of 14 exons and encodes a protein of 784 amino acids . The protein structure includes five extracellular cadherin repeats, a single transmembrane domain, and a highly conserved cytoplasmic tail .

Expression and Tissue Distribution

Cadherin 5 is predominantly expressed in endothelial cells, which line the interior surface of blood vessels. It is crucial for the formation and maintenance of intercellular junctions in the vascular endothelium . The expression of Cadherin 5 is tightly regulated during embryonic development and is essential for the proper formation of the vascular system .

Biological Functions

Cadherin 5 mediates calcium-dependent cell-cell adhesion, which is vital for maintaining the structural integrity of blood vessels. It plays a key role in:

  • Vascular permeability: Regulating the passage of molecules and cells across the endothelial barrier.
  • Angiogenesis: Formation of new blood vessels from pre-existing ones.
  • Endothelial cell survival: Preventing apoptosis and promoting cell survival .
Role in Immune Response and Pathogen Recognition

Cadherin 5 is involved in the immune response by regulating leukocyte transmigration across the endothelium. It interacts with various signaling molecules and receptors to modulate the immune response and maintain vascular homeostasis .

Mechanisms of Action

Cadherin 5 functions through homophilic interactions, where it binds to itself on adjacent cells to form adherens junctions. These junctions are linked to the actin cytoskeleton via catenins, which are cytoplasmic proteins that mediate the interaction between cadherins and the cytoskeleton .

Regulatory Mechanisms

The expression and function of Cadherin 5 are regulated by various signaling pathways, including the Wnt/β-catenin pathway, which modulates its transcription and stability. Additionally, post-translational modifications such as phosphorylation can influence its adhesive properties and interactions with other proteins .

Recombinant Cadherin 5

Recombinant Cadherin 5 (Mouse) is produced using an in vitro E. coli expression system. It is available in various forms, including lyophilized powder, and is used in research to study its biological functions and interactions .

Applications in Research

Recombinant Cadherin 5 is widely used in studies related to:

  • Vascular biology: Understanding the mechanisms of vascular development and diseases.
  • Cancer research: Investigating the role of endothelial cell adhesion in tumor angiogenesis and metastasis.
  • Immunology: Exploring the interactions between endothelial cells and immune cells .

Cadherin 5 is a critical molecule in vascular biology, and its recombinant form provides valuable insights into its functions and regulatory mechanisms.

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