Lead Inventor: Dr. B. Jack Longley Problem or Unmet Need: The skin is responsible for protecting the body from pathogens, temperature regulation, hair growth and vitamin production. Melanin, a brown pigment, is produced by melanocytes and taken up by...

Lead Inventor:
Dr. B. Jack Longley Problem or Unmet Need: The skin is responsible for protecting the body from pathogens, temperature regulation, hair growth and vitamin production. Melanin, a brown pigment, is produced by melanocytes and taken up by keratinocytes; the spectrum of human skin color is a result of melanin levels. Increasing evidence has shown that a tyrosine kinase receptor c-kit, and its ligand stem cell factor (SCF) play a major role in skin cell function. SCF has been shown to induce melanocyte proliferation, melanin production and migration. The Kit/SCF pathway regulates mast cells, which are repositories for inflammatory histamines, cytokines and anticoagulants. Melanocytes and mast cells can become cancerous and play a role in post-inflammatory hyperpigmentation and cutaneous inflammation. In contrast to humans, mice have few melanocytes in the epidermis, resulting in pale skin underneath their fur. Thus, mice are not useful as models for many human skin diseases, limiting research into pathogenesis and development of therapeutics. Details of the Invention: In humans, SCF is expressed by keratinocytes in the epidermis, leading to maintenance of the surrounding melanocyte population.
To generate a relevant mouse model, SCF was "knocked-into" a mouse line, under control of the human keratin 14 promoter. The resulting transgenic mice have significant skin pigmentation compared to littermates. Histology indicates that this is due to increased melanocyte activity in the epidermis. Also, preliminary studies show the mice develop hyperpigmentation after inflammation, suggesting the model may be useful for human disease.

Applications:

• A mouse model of post-inflammatory hyperpigmentation

• A mouse model of mastocytosis (proliferation of mast cells)

• A general mouse model of human skin, for research on auto-immune inflammation, oncogenesis or cell development Advantages:

• Activity of epidermal melanocytes mimics human skin cell population, one of the few models of human skin in a genetically tractable organism

• Transgenic mouse line can be further manipulated to understand effects of other genes on melanocytes and mast cells, such as growth factors and oncogenes

• Basic understanding of cutaneous inflammation pathology can speed drug discovery

• Topical and systemic therapies can be evaluated for efficacy, dosage and safety first in mice, rather than human or primate Opportunity: STV is actively seeking licensing partner(s) who will use the transgenic mouse model to develop therapies, biomarkers or pharmaceuticals for human skin disorders and cancer.

Early Stage

Publication #: US 2002-0123031 A1 WO 00/67794 US 2006-0216282 A

App. #: 09/306,143 09/474,478 PCT/US00/12405 09/980,572 11/314,421 12/291,462

Licensing or sponsored research support

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