Abstract
The leucine-rich repeats and immunoglobulin-like domains (LRIG) family includes transmembrane proteins known to be essential regulators of growth factor receptors like the epidermal growth factor receptor (EGFR/ERBB) family. As ERBBs are involved in cell proliferation, differentiation, death, motility, and adhesion, they are very versatile players during processes such as development, tissue homeostasis and tumorigenesis. The LRIG proteins are thought to regulate ERBBs and also other receptor tyrosine kinases. However, the role of LRIG proteins for regulatory feedback loops is not understood yet and requires further studies. To study LRIG1 in more detail, we generated doxycycline-inducible, skin-targeted (keratin 5 promoter-directed) transgenic (tg) mouse lines overexpressing LRIG1 using the TET-OFF system. As it is known that LRIG1-knockout mice develop a hyperplasia of the epidermis and psoriasis due to a hyperactive EGFR receptor, we anticipated a thinner epidermis in LRIG1 tg mice. Surprisingly, we could not obtain LRIG1 overexpressing mice in the expected rates. Only 9% (6/65) of all born mice were both LRIG1 and tTA positive and 83% (5/6) of these mice died immediately after birth. Only one double transgenic mouse survived for 13 days. The hair coat development of this animal was delayed and it showed reduced hair growth, hyperkeratosis, utricle development and a thicker epidermis compared with control siblings. Initial investigations in LRIG1 tg mice at day P0 suggest that the loricrin positive epidermal layer was increased in this animals. To study the phenotype of LRIG1 tg also in older animals, we suppressed the LRIG1 overexpression until birth by doxycycline treatment of pregnant females. Induction of the LRIG1 expression after birth by discontinued doxycycline application enables the survival of LRIG1 transgenic mice. These mice showed alopecia from three months of age with a significant thicker epidermis and utricles.
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