Hrhr scid Mouse Model for Xenograft Studies
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Solution Overview
Problem
Current breeding protocols for immunodeficient mouse models, such as athymic nude and NIH III mice, are inefficient as half of the offspring are not immunodeficient and thus unusable for xenograft studies due to reproductive issues and genetic variability, leading to a need for an improved breeding method to produce immunodeficient, hairless mice.
Innovation Solution
Breeding a mouse homozygous for a recessive hairless allele (Hr hr) with one homozygous for a Prkdc scid allele to produce hairless, immunodeficient mice that are both B-cell and T-cell deficient, allowing for homozygous breeding pairs and reducing unusable offspring, with the option to also include a beige allele for enhanced immunocompromised status.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If standard breeding practice for nude mice is used (mating homozygous male and heterozygous female), then immunodeficient hairless mice are produced, but half of the offspring are heterozygous and immunocompetent, making them unusable for xenograft studies
Solution Approach 1:
The patent combines two separate genetic traits (hairless Hr Hr and immunodeficient scid scid) into a single mouse model. By merging these traits through selective breeding, the invention creates a mouse that simultaneously exhibits both characteristics, eliminating the need to separate immunodeficient and hairless mice and thereby improving breeding efficiency while maintaining reliability.
Solution Approach 2:
The patent changes the genetic parameters of the mouse model by introducing the scid mutation alongside the existing Hr Hr mutation. This parameter change transforms the mouse from having only a hairless phenotype to having both hairless and severely immunodeficient phenotypes, enabling 100% of offspring to be usable for xenograft studies.
2Ease of manufacture
If homozygous female nude mice are used for breeding, then breeding is possible, but reproductive performance is poor due to irregular estrous cycle and limited lactation capacity
Solution Approach 1:
The patent creates a new mouse model that copies the essential immunodeficient phenotype needed for research while avoiding the reproductive defects of the original nude mouse model. The Hr Hr scid scid mouse replicates the T-cell deficiency and xenograft acceptance capability without inheriting the poor reproductive performance of homozygous nude females.
3Reliability
If heterozygous nude mice are used in xenograft studies, then they have normal coat and better health, but they are immunocompetent and reject foreign tissue and tumor transplants
Solution Approach 1:
The patent creates a composite genetic model combining Hr Hr and scid scid mutations. This composite genotype produces a mouse with both hairless phenotype and severe combined immunodeficiency, enabling the animal to accept xenografts while maintaining good health status. The combination of genetic elements achieves properties that neither mutation alone could provide.
Data Source
AI summary
The invention is directed to a hairless, immunodeficient mouse that is homozygous recessive for a hairless (Hrhr) allele and both B-cell deficient and T-cell deficient. The B-cell and T-cell deficiency is attributed to a homozygous recessive scid allele (Prkdcscid), a homozygous recessive beige allele (Lystbg), or a mutated Rag allele. These mice offer an advantage over nude mouse models used in cancer research because they can be maintained as homozygous breeding pairs and they have greater immune deficits, which permit better growth of xenogenic tumor lines, and rapid assessment of cutaneous and subcutaneous tumors and tissue grafts.