The HRas oncogene (HRAS), also known as the Harvey Rat Sarcoma Viral Oncogene Homolog (HRAS), is a member of the Ras oncogene family, which also includes KRAS and NRAS. All members of this family are associated with the development of mammalian sarcoma retroviruses ^[1]. HRAS encodes the H-Ras protein, a small GTPase responsible for transmitting signals from cell surface receptors to the nucleus, regulating cell proliferation, survival, and differentiation. HRAS is primarily expressed in various tissues, including the brain, heart, and skeletal muscle, and is involved in controlling the cellular response to growth factors. As a member of the small GTPase family, HRAS acts as a molecular switch, cycling between active and inactive states to influence key cellular processes. Mutations in the HRAS gene can lead to abnormal signal transduction, commonly found in tumors of stratified epithelial tissues, such as bladder cancer, thyroid cancer, and head and neck squamous cell carcinoma. Additionally, HRAS is associated with Costello syndrome, a genetic disorder characterized by developmental delays and an increased risk of tumors ^[2-3]. Early studies have shown that genotoxic carcinogens shorten the latency period and increase the incidence of malignant tumors in rasH2 mice, which carry the human HRAS (c-Ha-ras) oncogene, compared to non-transgenic mice. Therefore, rasH2 mice are ideal animal models for rapid carcinogenicity testing ^[4-5]. Further research has shown that F1 hybrid mice (CB6F1 background rasH2 mice) obtained by mating male C57BL/6J mice carrying the human prototype c-Ha-ras gene with female BALB/c mice are significantly more sensitive to both mutagenic and non-mutagenic carcinogens than control mice ^[5]. These mice are highly sensitive to the carcinogenicity of both genotoxic and non-genotoxic compounds while showing no response to non-carcinogens ^[6]. Between 12 to 18 months of age, rasH2 mice primarily develop spontaneous alveolar adenomas/bronchial adenomas/adenocarcinomas, splenic hemangiomas/hemangiosarcomas, and a smaller number of skin and gastric papillomas and lymphomas ^[4]. In the 1990s, this mouse model was officially approved by the FDA for carcinogenicity evaluations in drug safety assessments, reducing the standard two-year carcinogenicity test in common rodents to six months. The CB6F1-2*hHRAS mouse was obtained by mating double-genotype B6-Rosa26-hHRAS[KI/+]; H11-hHRAS[KI/+] mice with BALB/cAnCya mice. The double-genotype B6-Rosa26-hHRAS[KI/+]; H11-hHRAS[KI/+] mice were generated by crossing Rosa26-hHRAS mice (Catalog No.: I001213) with H11-hHRAS mice, both on the C57BL/6JCya background. This model carries two copies of the human proto-oncogene c-Ha-ras on a C57BL/6J × BALB/c hybrid background (i.e., CB6F1 background) and exhibits increased sensitivity to both genotoxic and non-genotoxic human carcinogens. CB6F1-2*hHRAS mice can be used for rapid in vivo testing of the carcinogenicity of genotoxic and non-genotoxic compounds, studying the impact of HRAS oncogene point mutations on tumorigenesis and development, and developing tumor prevention or suppression therapies.

The HRas oncogene (HRAS), also known as the Harvey Rat Sarcoma Viral Oncogene Homolog (HRAS), is a member of the Ras oncogene family, which also includes KRAS and NRAS. All members of this family are associated with the development of mammalian sarcoma retroviruses ^[1]. HRAS encodes the H-Ras protein, a small GTPase responsible for transmitting signals from cell surface receptors to the nucleus, regulating cell proliferation, survival, and differentiation. HRAS is primarily expressed in various tissues, including the brain, heart, and skeletal muscle, and is involved in controlling the cellular response to growth factors. As a member of the small GTPase family, HRAS acts as a molecular switch, cycling between active and inactive states to influence key cellular processes. Mutations in the HRAS gene can lead to abnormal signal transduction, commonly found in tumors of stratified epithelial tissues, such as bladder cancer, thyroid cancer, and head and neck squamous cell carcinoma. Additionally, HRAS is associated with Costello syndrome, a genetic disorder characterized by developmental delays and an increased risk of tumors ^[2-3]. Early studies have shown that genotoxic carcinogens shorten the latency period and increase the incidence of malignant tumors in rasH2 mice, which carry the human HRAS (c-Ha-ras) oncogene, compared to non-transgenic mice. Therefore, rasH2 mice are ideal animal models for rapid carcinogenicity testing ^[4-5]. Further research has shown that F1 hybrid mice (CB6F1 background rasH2 mice) obtained by mating male C57BL/6J mice carrying the human prototype c-Ha-ras gene with female BALB/c mice are significantly more sensitive to both mutagenic and non-mutagenic carcinogens than control mice ^[5]. These mice are highly sensitive to the carcinogenicity of both genotoxic and non-genotoxic compounds while showing no response to non-carcinogens ^[6]. Between 12 to 18 months of age, rasH2 mice primarily develop spontaneous alveolar adenomas/bronchial adenomas/adenocarcinomas, splenic hemangiomas/hemangiosarcomas, and a smaller number of skin and gastric papillomas and lymphomas ^[4]. In the 1990s, this mouse model was officially approved by the FDA for carcinogenicity evaluations in drug safety assessments, reducing the standard two-year carcinogenicity test in common rodents to six months. BALB/c;B6J-Rosa26-hHRAS mice are obtained by crossing Rosa26-hHRAS mice on a C57BL/6JCya background (Catalog No.: I001213) with BALB/cAnCya mice. This hybrid strain exhibits higher sensitivity to both genotoxic and non-genotoxic human carcinogens. BALB/c;B6J-Rosa26-hHRAS mice can be used for rapid in vivo testing of the carcinogenicity of genotoxic and non-genotoxic compounds, studying the impact of HRAS oncogene point mutations on tumorigenesis and development, and developing tumor prevention or suppression therapies.