1.Eradication of Aspiculuris tetraptera in various immunodeficient mouse models using ivermectin: a case report
Ji-Hun LEE ; Eun-Seon YOO ; Na-Won KIM ; Han-Bi JEONG ; Ah-Reum KANG ; Sun-Min SEO ; Young-Jun PARK ; Byeong-Cheol KANG ; Yang-Kyu CHOI
Laboratory Animal Research 2026;42(1):82-87
Background:
Despite advancements in laboratory animal facility management, pinworm infections remain a persistent issue in immunodeficient mouse colonies. Rapid diagnosis and treatment are crucial to mitigating potential scientific and economic consequences. Effective control requires both the administration of anthelmintic agents and rigorous environmental decontamination. However, the safety and efficacy of these treatments in genetically modified mouse models remains uncertain.Case presentation Aspiculuris tetraptera infestation was identified in multiple immunodeficient mouse models housed in a laboratory facility. Diagnosis was confirmed through fecal flotation for egg detection and necropsy for adult worm examination in the large intestines. Mice received three subcutaneous ivermectin injections at two-week intervals, coupled with environmental decontamination using ivermectin spray for four consecutive weeks. Following treatment, all colonies tested negative for A. tetraptera without any mortality.
Conclusions
A combination of subcutaneous ivermectin injection and environmental spray application effectively eradicated A. tetraptera infestation in immunodeficient mouse colonies. The treatment protocol led to the complete elimination of eggs and adult worms, offering a practical strategy for managing pinworm infections in genetically modified mouse models. Limitations include the small sample size, and the lack of a comprehensive evaluation of physiological and metabolic safety in immunodeficient mice. Further validation will be required to confirm the broader applicability of this approach.
2.Immune deficiency phenotypes of Il2rg, Rag2 or Il2rg/Rag2 double knockout rats;establishment of human leukemia xenograft models
Joo‑Il KIM ; Hyun‑Jin LIM ; Euna KWON ; Tomoji MASHIMO ; Byeong‑Cheol KANG
Laboratory Animal Research 2024;40(4):487-497
Background:
Genetically immunodeficient mice lacking Il2rg and Rag2 genes have been widely utilized in the field of biomedical research. However, immunodeficient rats, which offer the advantage of larger size, have not been as extensively used to date. Recently, Severe Combined Immunodeficiency (SCID) rats were generated using CRISPR/ Cas9 system, targeting Il2rg and Rag2 in National BioResource Project in Japan. We imported and investigated more detailed phenotypes of wild-type (WT) Il2rg knockout (KO), Rag2 KO and Il2rg/Rag2 KO rats for 20 weeks.
Results:
During experiments, Il2rg KO, Rag2 KO and Il2rg/Rag2 KO rats showed decreased white blood cells and sys‑ temic lymphopenia, with reduced CD4+, CD8+ T cells and CD161+ NK cells. Additionally, all KO strains exhibited reduced relative spleen weights, hypoplasia of the germinal center in the white pulp, and atrophy with the disap‑ pearance of the boundary between the cortex and medulla in the thymus, compared to WT rats. Furthermore, we established human acute lymphoblastic leukemia xenograft rat model by intravenously injecting 5.0 × 106 cells/kg of NALM6 cells into Il2rg/Rag2 KO rats.
Conclusions
These findings indicate that Il2rg KO, Rag2 KO, and Il2rg/Rag2 KO rats exhibited SCID phenotypes, sug‑ gesting their potential application as immunodeficient animal models for tumor xenograft studies.
3.Antigenicity evaluation of lac color and exploratory study for identifying potential biomarkers of anaphylaxis
Hyun‑Jin LIM ; Kang Min HAN ; Seung‑Hyun KIM ; Soo‑Kyung RYU ; Ji‑Ran YOU ; Jung‑Hee YOON ; Euna KWON ; Ji‑Eun KIM ; Byeong‑Cheol KANG
Laboratory Animal Research 2024;40(4):461-475
Background:
Lac color, a natural red dye derived from the larvae of laccifer lacca kerr, is one of the most commonly used substances in food. To date, no studies have reported on the antigenicity of lac color and the other biomarkers that can determine anaphylactic reactions. To address this, we evaluated the antigenicity of lac color through active systemic anaphylaxis (ASA) in addition to identifying potential biomarkers performing exploratory studies. For ASA test, Guinea pigs (n = 5) were sensitized with 0(negative control), 4 mg/kg of lac color, 4 mg/kg of lac color + FCA, and 5 mg/kg of ovalbumin + FCA (positive control) 3 times a week for three weeks. Fourteen days after the last sensi‑ tization, animals were challenged intravenously weekly for two weeks. Hematological and histopathological analyses were performed and compared to control groups.
Results:
In the ASA test, all lac color groups showed mild symptoms such as nose rubbing, urination, and evacuation, which are insufficient indicators of anaphylaxis. Exploratory studies identified several biomarkers: decreased platelet count, and increased basophil count; distention in the lung, and redness on the inner wall of trachea; mononuclear inflammatory cell infiltration (MICI) in the ear, and heart hemorrhage. When these biomarkers were applied to the ASA test of lac color, in comparison to the negative control group, the positive control group (ovalbumin + FCA) showed a significant over 60-fold reduction in platelet count and nearly threefold higher basophil count compared to other groups. Furthermore, only positive control group exhibited full lung distention and severe redness on the inner wall of the trachea. Mononuclear inflammatory cell infiltration (MICI) in the ear was about three times higher, and heart hemorrhage was only present in the positive control group compared to others. None of the lac color groups were different from the negative control group (p > 0.05), whereas the positive control group was significantly different (p < 0.05).
Conclusions
Our study concludes that lac color, at the tested concentrations, does not induce antigenicity in the guinea pig model, providing valuable safety data. Furthermore, the biomarkers identified in this study offer a supportive approach to evaluating the immunogenicity of substances in future research.
4.Immune deficiency phenotypes of Il2rg, Rag2 or Il2rg/Rag2 double knockout rats;establishment of human leukemia xenograft models
Joo‑Il KIM ; Hyun‑Jin LIM ; Euna KWON ; Tomoji MASHIMO ; Byeong‑Cheol KANG
Laboratory Animal Research 2024;40(4):487-497
Background:
Genetically immunodeficient mice lacking Il2rg and Rag2 genes have been widely utilized in the field of biomedical research. However, immunodeficient rats, which offer the advantage of larger size, have not been as extensively used to date. Recently, Severe Combined Immunodeficiency (SCID) rats were generated using CRISPR/ Cas9 system, targeting Il2rg and Rag2 in National BioResource Project in Japan. We imported and investigated more detailed phenotypes of wild-type (WT) Il2rg knockout (KO), Rag2 KO and Il2rg/Rag2 KO rats for 20 weeks.
Results:
During experiments, Il2rg KO, Rag2 KO and Il2rg/Rag2 KO rats showed decreased white blood cells and sys‑ temic lymphopenia, with reduced CD4+, CD8+ T cells and CD161+ NK cells. Additionally, all KO strains exhibited reduced relative spleen weights, hypoplasia of the germinal center in the white pulp, and atrophy with the disap‑ pearance of the boundary between the cortex and medulla in the thymus, compared to WT rats. Furthermore, we established human acute lymphoblastic leukemia xenograft rat model by intravenously injecting 5.0 × 106 cells/kg of NALM6 cells into Il2rg/Rag2 KO rats.
Conclusions
These findings indicate that Il2rg KO, Rag2 KO, and Il2rg/Rag2 KO rats exhibited SCID phenotypes, sug‑ gesting their potential application as immunodeficient animal models for tumor xenograft studies.
5.Antigenicity evaluation of lac color and exploratory study for identifying potential biomarkers of anaphylaxis
Hyun‑Jin LIM ; Kang Min HAN ; Seung‑Hyun KIM ; Soo‑Kyung RYU ; Ji‑Ran YOU ; Jung‑Hee YOON ; Euna KWON ; Ji‑Eun KIM ; Byeong‑Cheol KANG
Laboratory Animal Research 2024;40(4):461-475
Background:
Lac color, a natural red dye derived from the larvae of laccifer lacca kerr, is one of the most commonly used substances in food. To date, no studies have reported on the antigenicity of lac color and the other biomarkers that can determine anaphylactic reactions. To address this, we evaluated the antigenicity of lac color through active systemic anaphylaxis (ASA) in addition to identifying potential biomarkers performing exploratory studies. For ASA test, Guinea pigs (n = 5) were sensitized with 0(negative control), 4 mg/kg of lac color, 4 mg/kg of lac color + FCA, and 5 mg/kg of ovalbumin + FCA (positive control) 3 times a week for three weeks. Fourteen days after the last sensi‑ tization, animals were challenged intravenously weekly for two weeks. Hematological and histopathological analyses were performed and compared to control groups.
Results:
In the ASA test, all lac color groups showed mild symptoms such as nose rubbing, urination, and evacuation, which are insufficient indicators of anaphylaxis. Exploratory studies identified several biomarkers: decreased platelet count, and increased basophil count; distention in the lung, and redness on the inner wall of trachea; mononuclear inflammatory cell infiltration (MICI) in the ear, and heart hemorrhage. When these biomarkers were applied to the ASA test of lac color, in comparison to the negative control group, the positive control group (ovalbumin + FCA) showed a significant over 60-fold reduction in platelet count and nearly threefold higher basophil count compared to other groups. Furthermore, only positive control group exhibited full lung distention and severe redness on the inner wall of the trachea. Mononuclear inflammatory cell infiltration (MICI) in the ear was about three times higher, and heart hemorrhage was only present in the positive control group compared to others. None of the lac color groups were different from the negative control group (p > 0.05), whereas the positive control group was significantly different (p < 0.05).
Conclusions
Our study concludes that lac color, at the tested concentrations, does not induce antigenicity in the guinea pig model, providing valuable safety data. Furthermore, the biomarkers identified in this study offer a supportive approach to evaluating the immunogenicity of substances in future research.
6.Immune deficiency phenotypes of Il2rg, Rag2 or Il2rg/Rag2 double knockout rats;establishment of human leukemia xenograft models
Joo‑Il KIM ; Hyun‑Jin LIM ; Euna KWON ; Tomoji MASHIMO ; Byeong‑Cheol KANG
Laboratory Animal Research 2024;40(4):487-497
Background:
Genetically immunodeficient mice lacking Il2rg and Rag2 genes have been widely utilized in the field of biomedical research. However, immunodeficient rats, which offer the advantage of larger size, have not been as extensively used to date. Recently, Severe Combined Immunodeficiency (SCID) rats were generated using CRISPR/ Cas9 system, targeting Il2rg and Rag2 in National BioResource Project in Japan. We imported and investigated more detailed phenotypes of wild-type (WT) Il2rg knockout (KO), Rag2 KO and Il2rg/Rag2 KO rats for 20 weeks.
Results:
During experiments, Il2rg KO, Rag2 KO and Il2rg/Rag2 KO rats showed decreased white blood cells and sys‑ temic lymphopenia, with reduced CD4+, CD8+ T cells and CD161+ NK cells. Additionally, all KO strains exhibited reduced relative spleen weights, hypoplasia of the germinal center in the white pulp, and atrophy with the disap‑ pearance of the boundary between the cortex and medulla in the thymus, compared to WT rats. Furthermore, we established human acute lymphoblastic leukemia xenograft rat model by intravenously injecting 5.0 × 106 cells/kg of NALM6 cells into Il2rg/Rag2 KO rats.
Conclusions
These findings indicate that Il2rg KO, Rag2 KO, and Il2rg/Rag2 KO rats exhibited SCID phenotypes, sug‑ gesting their potential application as immunodeficient animal models for tumor xenograft studies.
7.Antigenicity evaluation of lac color and exploratory study for identifying potential biomarkers of anaphylaxis
Hyun‑Jin LIM ; Kang Min HAN ; Seung‑Hyun KIM ; Soo‑Kyung RYU ; Ji‑Ran YOU ; Jung‑Hee YOON ; Euna KWON ; Ji‑Eun KIM ; Byeong‑Cheol KANG
Laboratory Animal Research 2024;40(4):461-475
Background:
Lac color, a natural red dye derived from the larvae of laccifer lacca kerr, is one of the most commonly used substances in food. To date, no studies have reported on the antigenicity of lac color and the other biomarkers that can determine anaphylactic reactions. To address this, we evaluated the antigenicity of lac color through active systemic anaphylaxis (ASA) in addition to identifying potential biomarkers performing exploratory studies. For ASA test, Guinea pigs (n = 5) were sensitized with 0(negative control), 4 mg/kg of lac color, 4 mg/kg of lac color + FCA, and 5 mg/kg of ovalbumin + FCA (positive control) 3 times a week for three weeks. Fourteen days after the last sensi‑ tization, animals were challenged intravenously weekly for two weeks. Hematological and histopathological analyses were performed and compared to control groups.
Results:
In the ASA test, all lac color groups showed mild symptoms such as nose rubbing, urination, and evacuation, which are insufficient indicators of anaphylaxis. Exploratory studies identified several biomarkers: decreased platelet count, and increased basophil count; distention in the lung, and redness on the inner wall of trachea; mononuclear inflammatory cell infiltration (MICI) in the ear, and heart hemorrhage. When these biomarkers were applied to the ASA test of lac color, in comparison to the negative control group, the positive control group (ovalbumin + FCA) showed a significant over 60-fold reduction in platelet count and nearly threefold higher basophil count compared to other groups. Furthermore, only positive control group exhibited full lung distention and severe redness on the inner wall of the trachea. Mononuclear inflammatory cell infiltration (MICI) in the ear was about three times higher, and heart hemorrhage was only present in the positive control group compared to others. None of the lac color groups were different from the negative control group (p > 0.05), whereas the positive control group was significantly different (p < 0.05).
Conclusions
Our study concludes that lac color, at the tested concentrations, does not induce antigenicity in the guinea pig model, providing valuable safety data. Furthermore, the biomarkers identified in this study offer a supportive approach to evaluating the immunogenicity of substances in future research.
8.Immune deficiency phenotypes of Il2rg, Rag2 or Il2rg/Rag2 double knockout rats;establishment of human leukemia xenograft models
Joo‑Il KIM ; Hyun‑Jin LIM ; Euna KWON ; Tomoji MASHIMO ; Byeong‑Cheol KANG
Laboratory Animal Research 2024;40(4):487-497
Background:
Genetically immunodeficient mice lacking Il2rg and Rag2 genes have been widely utilized in the field of biomedical research. However, immunodeficient rats, which offer the advantage of larger size, have not been as extensively used to date. Recently, Severe Combined Immunodeficiency (SCID) rats were generated using CRISPR/ Cas9 system, targeting Il2rg and Rag2 in National BioResource Project in Japan. We imported and investigated more detailed phenotypes of wild-type (WT) Il2rg knockout (KO), Rag2 KO and Il2rg/Rag2 KO rats for 20 weeks.
Results:
During experiments, Il2rg KO, Rag2 KO and Il2rg/Rag2 KO rats showed decreased white blood cells and sys‑ temic lymphopenia, with reduced CD4+, CD8+ T cells and CD161+ NK cells. Additionally, all KO strains exhibited reduced relative spleen weights, hypoplasia of the germinal center in the white pulp, and atrophy with the disap‑ pearance of the boundary between the cortex and medulla in the thymus, compared to WT rats. Furthermore, we established human acute lymphoblastic leukemia xenograft rat model by intravenously injecting 5.0 × 106 cells/kg of NALM6 cells into Il2rg/Rag2 KO rats.
Conclusions
These findings indicate that Il2rg KO, Rag2 KO, and Il2rg/Rag2 KO rats exhibited SCID phenotypes, sug‑ gesting their potential application as immunodeficient animal models for tumor xenograft studies.
9.Antigenicity evaluation of lac color and exploratory study for identifying potential biomarkers of anaphylaxis
Hyun‑Jin LIM ; Kang Min HAN ; Seung‑Hyun KIM ; Soo‑Kyung RYU ; Ji‑Ran YOU ; Jung‑Hee YOON ; Euna KWON ; Ji‑Eun KIM ; Byeong‑Cheol KANG
Laboratory Animal Research 2024;40(4):461-475
Background:
Lac color, a natural red dye derived from the larvae of laccifer lacca kerr, is one of the most commonly used substances in food. To date, no studies have reported on the antigenicity of lac color and the other biomarkers that can determine anaphylactic reactions. To address this, we evaluated the antigenicity of lac color through active systemic anaphylaxis (ASA) in addition to identifying potential biomarkers performing exploratory studies. For ASA test, Guinea pigs (n = 5) were sensitized with 0(negative control), 4 mg/kg of lac color, 4 mg/kg of lac color + FCA, and 5 mg/kg of ovalbumin + FCA (positive control) 3 times a week for three weeks. Fourteen days after the last sensi‑ tization, animals were challenged intravenously weekly for two weeks. Hematological and histopathological analyses were performed and compared to control groups.
Results:
In the ASA test, all lac color groups showed mild symptoms such as nose rubbing, urination, and evacuation, which are insufficient indicators of anaphylaxis. Exploratory studies identified several biomarkers: decreased platelet count, and increased basophil count; distention in the lung, and redness on the inner wall of trachea; mononuclear inflammatory cell infiltration (MICI) in the ear, and heart hemorrhage. When these biomarkers were applied to the ASA test of lac color, in comparison to the negative control group, the positive control group (ovalbumin + FCA) showed a significant over 60-fold reduction in platelet count and nearly threefold higher basophil count compared to other groups. Furthermore, only positive control group exhibited full lung distention and severe redness on the inner wall of the trachea. Mononuclear inflammatory cell infiltration (MICI) in the ear was about three times higher, and heart hemorrhage was only present in the positive control group compared to others. None of the lac color groups were different from the negative control group (p > 0.05), whereas the positive control group was significantly different (p < 0.05).
Conclusions
Our study concludes that lac color, at the tested concentrations, does not induce antigenicity in the guinea pig model, providing valuable safety data. Furthermore, the biomarkers identified in this study offer a supportive approach to evaluating the immunogenicity of substances in future research.
10.Immune deficiency phenotypes of Il2rg, Rag2 or Il2rg/Rag2 double knockout rats;establishment of human leukemia xenograft models
Joo‑Il KIM ; Hyun‑Jin LIM ; Euna KWON ; Tomoji MASHIMO ; Byeong‑Cheol KANG
Laboratory Animal Research 2024;40(4):487-497
Background:
Genetically immunodeficient mice lacking Il2rg and Rag2 genes have been widely utilized in the field of biomedical research. However, immunodeficient rats, which offer the advantage of larger size, have not been as extensively used to date. Recently, Severe Combined Immunodeficiency (SCID) rats were generated using CRISPR/ Cas9 system, targeting Il2rg and Rag2 in National BioResource Project in Japan. We imported and investigated more detailed phenotypes of wild-type (WT) Il2rg knockout (KO), Rag2 KO and Il2rg/Rag2 KO rats for 20 weeks.
Results:
During experiments, Il2rg KO, Rag2 KO and Il2rg/Rag2 KO rats showed decreased white blood cells and sys‑ temic lymphopenia, with reduced CD4+, CD8+ T cells and CD161+ NK cells. Additionally, all KO strains exhibited reduced relative spleen weights, hypoplasia of the germinal center in the white pulp, and atrophy with the disap‑ pearance of the boundary between the cortex and medulla in the thymus, compared to WT rats. Furthermore, we established human acute lymphoblastic leukemia xenograft rat model by intravenously injecting 5.0 × 106 cells/kg of NALM6 cells into Il2rg/Rag2 KO rats.
Conclusions
These findings indicate that Il2rg KO, Rag2 KO, and Il2rg/Rag2 KO rats exhibited SCID phenotypes, sug‑ gesting their potential application as immunodeficient animal models for tumor xenograft studies.

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