Catalog Number: C001532
Strain Name: C57BL/6JCya-Serping1em1/Cya
Genetic Background: C57BL/6JCya
Reproduction: Homozygote x Homozygote
Strain Description
The SERPING1 gene encodes a highly glycosylated plasma protein involved in regulating the complement cascade. The complement C1 inhibitor (C1-INH) produced by this gene is a crucial multifunctional plasma glycoprotein that plays key roles in various biological systems, including the complement system, coagulation system, and fibrinolytic system. Despite its essential role in multiple physiological processes, C1-INH is known for its defect in hereditary angioedema (HAE). HAE, also known as C1 inhibitor deficiency, is a rare and debilitating disease. Patients with HAE experience severe periodic swelling, primarily affecting the arms, legs, face, intestines, and respiratory tract. The prevalence of HAE is approximately 1 in 50,000 individuals, and if left untreated, it can lead to a mortality rate of 20% to 30% when it affects the respiratory tract [1]. SERPING1 is the primary pathogenic gene in hereditary angioedema (HAE). Mutations in this gene lead to the deficiency or dysfunction of complement C1 inhibitor (C1-INH). As a result, there is an excessive secretion of vasoactive peptides, causing fluid leakage into tissues such as mucous membranes and subcutaneous areas, leading to localized swelling and edema [2]. As an essential protein for maintaining immune balance and preventing excessive inflammatory responses, C1-INH has been gaining widespread attention due to its pathogenic mechanisms, as well as its role in drug development. Serping1 gene-deficient mice serve as crucial tools for researching C1 inhibitor deficiency.
This model is Serping1 gene knockout mice, where the Serping1 gene homologous to the human SERPING1 gene has been knocked out. In Serping1 KO mice, C1-INH protein is deficient. This leads to a significant increase in vascular permeability, which closely mirrors the pathogenic mechanisms and clinical symptoms observed in human HAE patients. The homozygous mice are viable and fertile. Serping1 KO mice serve as valuable tools for studying the pathogenesis of HAE and screening therapeutic drugs.
The Serping1 gene is located on mouse chromosome 2, and a partial sequence (c.159_168 TCCCCCAGAG) in exon 3 was knocked out.
● Pathogenesis of hereditary angioedema (HAE) and development of therapeutic drugs for HAE;
● Research on complement systems, coagulation systems, and anti-inflammation.
1. Serping1 KO mice lack expression of the Serping1 gene
Figure 1. RT-qPCR detection of Serping1 gene expression in 7-week-old Serping1 KO and wild-type (WT) mice. The results indicate that, compared to wild-type mice, the Serping1 gene is virtually unexpressed in the white adipose tissue of Serping1 KO mice, and its expression is significantly reduced in the liver and lungs. Homozygous Serping1 KO mice exhibit minimal expression of Serping1 transcripts, with only a small amount of undegraded nonsense RNA detected. This gene no longer encodes a full-length functional protein.
(ND: Not detected)
2. Serping1 KO mice have increased vascular permeability in the mouth, nose, forepaw, and hind paw
Figure 2. Evans Blue (EB)* staining in Serping1 KO mice and wild-type (WT) mice for the mouth, nose, forepaws, and hind paws. To assess in vivo vascular permeability, EB was intravenously injected into 9-week-old mice (15mg/kg in 100µL PBS) via the tail vein, and mouse appearances were photographed every 5 minutes. The results indicate that over time, the nose and forepaws of Serping1 KO mice gradually darken, while the color remains unchanged in wild-type mice, suggesting a significant increase in vascular permeability in Serping1 KO mice (Figure a). Similarly, at 10 weeks of age, vascular permeability was observed using the same tail vein injection of EB, and photos were taken 30 minutes later. The results show that compared to wild-type mice, the color change in the nose, forepaws, and hind paws of Serping1 KO mice is deeper, indicating a noticeable increase in vascular permeability (Figure b).
*Evans Blue (EB) is a commonly used dye for in vivo assessment of vascular permeability, allowing quantification of vascular leakage and observation of vascular permeability in live mice.
3. Infiltration of organs by vascular material in the presence of Serping1 KO mice
Figure 3. Extravasation in different tissues of 10-week-old Serping1 KO mice. After intravenous injection of EB dye via the tail vein for 30 minutes, the mice were euthanized, and tissues such as the heart, spleen, lungs, kidneys, small intestine, and rear paws were perfused and collected for further processing. Following the completion of the procedure, the optical density (OD) values of the corresponding sample solutions were measured to quantify the EB dye content in various tissues. The results indicate that Serping1 KO mice exhibit varying degrees of EB dye leakage in different tissues, suggesting that the increased vascular permeability in these mice leads to significant infiltration of EB dye from blood vessels into other tissues.
Reference
[1] Busse PJ, Christiansen SC. Hereditary Angioedema. N Engl J Med. 2020 Mar 19;382(12):1136-1148.
[2] Genetics Home Reference. (n.d.). Hereditary Angioedema. Retrieved January 5, 2024, from https://medlineplus.gov/genetics/condition/hereditary-angioedema/#frequency