Name: MRL/MpJ-Fas-KO Mouse
Brand: サイヤジェン（Cyagen）
SKU: C001602

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MRL/MpJ-Fas-KO Mouse

製品名

MRL/MpJ-Fas-KO Mouse

製品ID

C001602

系統名

MRL/MpJ-Fas^em1/Cya

背景情報

MRL/MpJ

状況

このマウス系統を論文で使用する場合は、「MRL/MpJ-Fas-KO Mouse（カタログ番号C001602）はサイアジェンから購入しました。」と引用してください。

Disease Animal Models

Systemic Lupus Erythematosus

製品タイプ

年齢

遺伝子型

性別

数量

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Disease Animal Models

Systemic Lupus Erythematosus

基本情報

検証 Data

系統詳細

The Fas cell surface death receptor (FAS), also known as CD95 or TNFRSF6, is a type I transmembrane protein in the tumor necrosis factor receptor superfamily^[1]. It plays a key role in apoptosis by transmitting signals that initiate programmed cell death. Expressed across various tissues such as immune cells, liver, heart, and skin, FAS regulates cellular homeostasis. Upon binding with its ligand (FASL), FAS oligomerizes to form the death-inducing signaling complex (DISC), activating caspases that execute apoptosis. This is crucial for immune homeostasis, tissue maintenance, and removing damaged or infected cells. Dysregulated FAS-mediated apoptosis can lead to autoimmune disorders (e.g., autoimmune lymphoproliferative syndrome) or contribute to cancer development by enabling uncontrolled cell proliferation^[1-3].

The MRL/MpJ Strain (Murphy Roths Large), derived from a complex cross between several strains (LG/J, AKR/J, C3H/Di, C57BL/6), was established for autoimmune disease research. They serve as controls in studies of the MRL/MpJ-Faslpr strain, a mouse model with premature termination of gene transcription and abnormal mRNA splicing due to lymphoproliferation (lpr) spontaneous mutation of the Fas gene, which develops lupus-like autoimmune disease^[4]. MRL/MpJ mice are vital in studying autoimmune conditions (e.g., Sjögren syndrome, autoimmune arthritis, lupus erythematosus, hearing defects) and are notable for their scarless tissue regeneration capabilities. This makes them valuable models for research in tissue regeneration, wound healing, autoimmune diseases, muscle dystrophy, and hearing loss^[4-6].

The MRL/MpJ-Fas knockout (KO) mouse model, generated via targeted deletion of the Fas gene in MRL/MpJ mice, provides a critical tool for investigating the role of FAS in autoimmune pathologies. This model furnishes a critical system for elucidating the etiology of systemic lupus erythematosus (SLE) and identifying potential therapeutic targets within the FAS signaling cascade for the treatment of autoimmune disorders.

参考文献

Volpe E, Sambucci M, Battistini L, Borsellino G. Fas-Fas Ligand: Checkpoint of T Cell Functions in Multiple Sclerosis. Front Immunol. 2016 Sep 27;7:382.

Opferman JT. Apoptosis in the development of the immune system. Cell Death Differ. 2008 Feb;15(2):234-42.

de Oliveira GL, Malmegrim KC, Ferreira AF, Tognon R, Kashima S, Couri CE, Covas DT, Voltarelli JC, de Castro FA. Up-regulation of fas and fasL pro-apoptotic genes expression in type 1 diabetes patients after autologous haematopoietic stem cell transplantation. Clin Exp Immunol. 2012 Jun;168(3):291-302.

Adachi M, Watanabe-Fukunaga R, Nagata S. Aberrant transcription caused by the insertion of an early transposable element in an intron of the Fas antigen gene of lpr mice. Proc Natl Acad Sci U S A. 1993 Mar 1;90(5):1756-60.

Heydemann A. The super super-healing MRL mouse strain. Front Biol (Beijing). 2012 Dec 1;7(6):522-538.

Velasco C, Dunn C, Sturdy C, Izda V, Martin J, Rivas A, McNaughton J, Jeffries MA. Ear wound healing in MRL/MpJ mice is associated with gut microbiome composition and is transferable to non-healer mice via microbiome transplantation. PLoS One.

系統作製戦略

The sequence of exons 2-4 of the Fas gene was knocked out in MRL/MpJ mice by gene editing technology.

Figure 1. Gene editing strategy for MRL/MpJ-Fas-KO mice.

適用分野

Systemic Lupus Erythematosus (SLE) research;

Immunology and inflammation-related research;

Other autoimmune research (Sjögren’s syndrome, Rheumatoid Arthritis, etc.).

検証 Data

1. Gene Expression

RT-qPCR results showed that the expression of murine Fas mRNA was not detected in the kidney tissues of female MRL/MpJ-Fas-KO mice, whereas murine Fas expression was detectable in female MRL/MpJ mice. This result confirmed the absence of murine Fas mRNA expression in MRL/MpJ-Fas-KO mice. (Data are presented as mean ± standard deviation.)

Figure 2. Gene Expression Detection in Kidney Tissues of MRL/MpJ-Fas-KO Mice and MRL/MpJ Mice (Female, n=3, 10–14W).

2. Mouse Group Information and Testing Items

Figure 3. Mouse Group Allocation and Assayed Parameters.

3. Body Weight, Survival Curves, and Urinary Albumin-to-Creatinine Ratio (UACR)

1. No significant difference was observed in the body weight of male mice among all groups. The body weight of female MRL/MpJ-Fas-KO and MRL/MpJ-Fas^lpr mice was increased compared with that of female MRL/MpJ mice, which was associated with lymphadenopathy. (mean ± SD)

2. Compared with age-matched MRL/MpJ mice, individual female MRL/MpJ-Fas^lpr and MRL/MpJ-Fas-KO mice first exhibited a UACR value above 300 mg/g at 13–14 weeks of age. The UACR of female MRL/MpJ-Fas-KO mice was significantly elevated compared with the control group from week 20 onwards, while that of female MRL/MpJ-Fas^lpr mice showed a significant increase from week 23 onwards. UACR results indicated the occurrence of renal lesions in the model mice, with a large individual variation among mice within the same group. (Two-way ANOVA, mean ± SD)

3. By week 26, mortality was observed in all MRL/MpJ-Fas-KO and MRL/MpJ-Fas^lpr mouse groups, among which female MRL/MpJ-Fas-KO mice had the highest mortality rate.

Figure 4. Body Weight, Survival Curve, and Urinary Albumin-to-Creatinine Ratio (UACR) Results of MRL/MpJ-Fas-KO Mice, MRL/MpJ-Fas^lpr Mice, and MRL/MpJ Mice.

4. Lymph Node Score

1. Lymphadenopathy was first observed in individual female MRL/MpJ-Fas-KO and MRL/MpJ-Fas^lpr mice at 9 weeks of age, involving the cervical, axillary, brachial, and inguinal regions. By 12 weeks of age, lymphadenopathy was present in nearly all mice of the above strains. Lymph node scores increased with advancing age, and female MRL/MpJ-Fas-KO mice exhibited the most severe lymphadenopathy at 26 weeks of age. (mean ± SD)

2. The affected regions of lymphadenopathy varied among individual mice, with involvement of one or more sites among the cervical, axillary, brachial, and inguinal regions.

Figure 5. Gross Morphology Images and Lymph Node Scores of MRL/MpJ-Fas-KO Mice, MRL/MpJ-Fas^lpr Mice, and MRL/MpJ Mice.

5. Skin Score

1. Skin lesions (involving the facial, auricular, dorsal, and scapular regions) were first observed in female MRL/MpJ-Fas-KO and MRL/MpJ-Fas^lpr mice at 14–15 weeks of age. Overall, the severity of skin ulceration in MRL/MpJ-Fas-KO mice was higher than that in MRL/MpJ-Fas^lpr mice. (mean ± SD)

2. Mice developed single or multiple skin lesion foci on the face, ears, or back, accompanied by ulceration and crusting. At the mild stage of the disease, such lesions were observed to exhibit a trend of spontaneous remission. Individual variations were noted among mice within the same group.

3. The scores represented the average skin lesion status of the overall group, while skin lesions were not present in every individual mouse. The incidence of skin lesions in each group at week 26 is shown in the table.

Figure 6. Gross Morphology Images and Skin Scores of MRL/MpJ-Fas-KO Mice, MRL/MpJ-Fas^lpr Mice, and MRL/MpJ Mice.

6. Complete Blood Count (CBC)

1. Compared with female MRL/MpJ mice, the counts of peripheral blood white blood cells (WBC) and lymphocytes (Lym) were elevated in female MRL/MpJ-Fas-KO and MRL/MpJ-Fas^lpr mice (Reason: Fas protein dysfunction leads to impaired clearance of autoreactive and activated lymphocytes). (mean ± SD)

2. Compared with female MRL/MpJ mice, the levels of hemoglobin (HGB) and platelets (PLT) were decreased in female MRL/MpJ-Fas-KO and MRL/MpJ-Fas^lpr mice (Reason: Autoantibodies against red blood cells/platelets produced by autoreactive B cells mediate phagocytic destruction by macrophages). (mean ± SD)

Figure 7. Complete Blood Count (CBC) Results of MRL/MpJ-Fas-KO Mice, MRL/MpJ-Fas^lpr Mice, and MRL/MpJ Mice.

7. Organ Index

（1）Spleen Index

Results showed that the spleen index was elevated in MRL/MpJ-Fas-KO and MRL/MpJ-Fas^lpr mice compared with MRL/MpJ mice. (mean ± SD; SW/BW (%): Spleen Weight/Body Weight*100%)

Figure 8. Gross Anatomical Morphology of the Spleen and Spleen Index in MRL/MpJ-Fas-KO Mice, MRL/MpJ-Fas^lpr Mice, and MRL/MpJ Mice.

（2）Lymph Node Index

Results showed that the lymph node index (axillary lymph nodes) was elevated in MRL/MpJ-Fas-KO and MRL/MpJ-Fas^lpr mice compared with MRL/MpJ mice. (mean ± SD; LNW/BW (%): Lymph Node Weight/Body Weight*100%)

Figure 9. Gross Anatomical Morphology of Lymph Nodes and Lymph Node Index in MRL/MpJ-Fas-KO Mice, MRL/MpJ-Fas^lpr Mice, and MRL/MpJ Mice.

（3）Kidney Index

Results showed that the kidney index tended to increase in female MRL/MpJ-Fas-KO and MRL/MpJ-Fas^lpr mice compared with female MRL/MpJ mice. (mean ± SD; KW/BW (%): Kidney Weight/Body Weight*100%)

Figure 10. Gross Anatomical Morphology of the Kidneys and Kidney Index in MRL/MpJ-Fas-KO Mice, MRL/MpJ-Fas^lpr Mice, and MRL/MpJ Mice.

8. Renal Pathological Analysis

（1）Glomerulus & Renal Tubule

Pathological evaluation of renal H&E staining revealed that severe pathological changes of lupus nephritis were observed in the glomeruli and renal tubules of both MRL/MpJ-Fas-KO and MRL/MpJ-Fas^lpr mice, with comparable severity between the two strains. In comparison with MRL/MpJ mice, the two model strains exhibited more severe renal injury. (mean ± SD)

Figure 11. Pathological Analysis of Glomeruli and Renal Tubules in MRL/MpJ-Fas-KO Mice, MRL/MpJ-Fas^lpr Mice, and MRL/MpJ Mice*. *Mesangial proliferation (yellow arrow); glomerulosclerosis (green arrow); cellular crescent formation (blue arrow); fibrous crescent formation (cyan arrow); focal tubular atrophy (white arrow); mild tubular degeneration (red arrow); tubular casts (pentagram).

（2）Renal Artery & Renal Interstitium

Pathological evaluation of renal H&E staining indicated that severe pathological changes of lupus nephritis were present in the renal arteries and renal interstitium of both MRL/MpJ-Fas-KO and MRL/MpJ-Fas^lpr mice, with comparable lesion severity between the two strains. In comparison with MRL/MpJ mice, the two model strains exhibited more severe renal injury. (mean ± SD)

Figure 12. Pathological Analysis of Renal Arteries and Renal Interstitium in MRL/MpJ-Fas-KO Mice, MRL/MpJ-Fas^lpr Mice, and MRL/MpJ Mice*. *Perivascular inflammation and interstitial inflammation (black arrow); mild tubular degeneration (red arrow); vascular degeneration (gray arrow); interstitial fibrosis (orange arrow).

（3）Renal Disease Score

By week 26, the renal lesion scores of MRL/MpJ mice indicated that the lesions remained in a reversible stage dominated by active inflammation. In contrast, the renal scores of MRL/MpJ-Fas-KO and MRL/MpJ-Fas^lpr mice showed that the chronic score was dominant or comparable to the activity score, demonstrating that their lesions had progressed to an advanced or end-stage characterized by irreversible fibrosis and sclerosis. Renal disease score results were similar between the two model strains, and no gender difference was observed at this stage. (mean ± SD)

Figure 13. Renal Disease Scoring Criteria and Results of MRL/MpJ-Fas-KO Mice, MRL/MpJ-Fas^lpr Mice, and MRL/MpJ Mice.

（4）Pathological Classification

1.Pathological classification at week 26 revealed that renal lesions in MRL/MpJ mice remained at the stage of Type Ⅲ/Ⅳ (Proliferative), while those in the two gene-deficient model strains (MRL/MpJ-Fas-KO and MRL/MpJ-Fas^lpr) had progressed to advanced or end-stage lesions dominated by Type V/VI, with only individual MRL/MpJ-Fas^lpr mice as exceptions (still Type Ⅲ).

2.The renal lesion classifications of the two model strains were highly similar.

Figure 14. Pathological Classification of MRL/MpJ-Fas-KO Mice, MRL/MpJ-Fas^lpr Mice, and MRL/MpJ Mice.

MRL/MpJ-Fas-KO Mouse

基本情報

検証 Data

関連リソース

遺伝子名

遺伝子別名

NCBI ID

染色体

MGI ID

さらに

データシート

系統詳細

参考文献

系統作製戦略

適用分野

1. Gene Expression

2. Mouse Group Information and Testing Items

3. Body Weight, Survival Curves, and Urinary Albumin-to-Creatinine Ratio (UACR)

4. Lymph Node Score

5. Skin Score

6. Complete Blood Count (CBC)

7. Organ Index

8. Renal Pathological Analysis

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