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Published on: September 7, 2013
SKHIN/Sprd, a new genetically defined inbred hairless mouse strain for UV-induced skin carcinogenesis studies
Carlos Perez1, Jan Parker-Thornburg, Carol Mikulec
1Department of Molecular Carcinogenesis, The University of Texas M. D. Anderson Cancer Center, Smithville, TX 78957, USA.
Abstract:
Strains of mice vary in their susceptibility to ultra-violet (UV) radiation-induced skin tumors. Some strains of hairless mice (homozygous for the spontaneous Hr(hr) mutation) are particularly susceptible to these tumors. The skin tumors that develop in hairless mice resemble, both at the morphologic and molecular levels, UV-induced squamous cell carcinomas (SCC) and their precursors in human. The most commonly employed hairless mice belong to the SKH1 stock. However, these mice are outbred and their genetic background is not characterized, which makes them a poor model for genetic studies. We have developed a new inbred strain from outbred SKH1 mice that we named SKHIN/Sprd (now at generation F31). In order to characterize the genetic background of this new strain, we genotyped a cohort of mice at F30 with 92 microsatellites and 140 single nucleotide polymorphisms (SNP) evenly distributed throughout the mouse genome. We also exposed SKHIN/Sprd mice to chronic UV irradiation and showed that they are as susceptible to UV-induced skin carcinogenesis as outbred SKH1 mice. In addition, we proved that, albeit with low efficiency, inbred SKHIN/Sprd mice are suitable for transgenic production by classical pronuclear microinjection. This new inbred strain will be useful for the development of transgenic and congenic strains on a hairless inbred background as well as the establishment of syngeneic tumor cell lines. These new tools can potentially help elucidate a number of features of the cutaneous response to UV irradiation in humans, including the effect of genetic background and modifier genes.
Insights
Researchers developed a new inbred hairless mouse strain (SKHIN/Sprd) that mirrors human skin cancer development after UV exposure. This genetically characterized strain is crucial for advancing skin cancer research and developing new therapies.
Area of Science:
- Dermatology and Carcinogenesis
- Genetics and Animal Models
Background:
- Hairless mouse strains, particularly SKH1, are susceptible to ultraviolet (UV) radiation-induced skin tumors, mimicking human squamous cell carcinomas (SCC).
- Outbred SKH1 mice, commonly used, lack a characterized genetic background, limiting their utility in genetic studies of skin carcinogenesis.
- A need exists for a genetically defined, hairless mouse model to study UV-induced skin cancer mechanisms.
Purpose of the Study:
- To develop and characterize a new inbred hairless mouse strain (SKHIN/Sprd) from the outbred SKH1 stock.
- To assess the genetic background and susceptibility of the SKHIN/Sprd strain to UV radiation-induced skin carcinogenesis.
- To evaluate the suitability of the SKHIN/Sprd strain for transgenic applications.
Main Methods:
- Development of an inbred strain (SKHIN/Sprd) from outbred SKH1 mice through selective breeding to generation F31.
- Genotyping of F30 generation SKHIN/Sprd mice using 92 microsatellites and 140 single nucleotide polymorphisms (SNPs) across the genome.
- Exposure of SKHIN/Sprd mice to chronic UV irradiation to assess skin tumor development and susceptibility.
- Evaluation of transgenic production efficiency via pronuclear microinjection in inbred SKHIN/Sprd mice.
Main Results:
- The new SKHIN/Sprd strain was successfully established and inbred to generation F31.
- Genotyping confirmed a characterized genetic background for the SKHIN/Sprd strain.
- SKHIN/Sprd mice exhibited susceptibility to UV-induced skin carcinogenesis comparable to outbred SKH1 mice.
- Inbred SKHIN/Sprd mice demonstrated suitability, albeit with low efficiency, for transgenic production.
Conclusions:
- The SKHIN/Sprd inbred hairless mouse strain provides a genetically defined model for UV radiation-induced skin cancer research.
- This strain is valuable for developing transgenic and congenic models and syngeneic tumor cell lines.
- The SKHIN/Sprd model will aid in understanding the role of genetic background and modifier genes in cutaneous UV responses relevant to human skin cancer.
