The Role of a Novel Gene in a Murine Hair Loss Model

The Role of a Novel Gene in a Murine Hair Loss Model
Tongyu Cao, Ph.D.

My laboratory uses the lab mice as model systems to investigate the causes of hair loss.  We study hair follicle development in normal mice as well as hair loss in mutant mice, using molecular and cell biology approaches.  Our current model is a mutant strain called rough coat (rc).  The rc mutation occurred naturally, and is recessive; only mice that carry two copies of the mutant gene show the abnormalities.  Homozygous rc mice start to show unkempt hair coat about two weeks after birth, and develop hair loss thereafter.  Abnormal pigmentation occurs sometimes when the hair grows back, as seen in some alopecia patients.  In order to understand the genetic basis of hair loss in these mice, we carried out positional cloning to identify the gene mutation. 

We identified a point mutation in Mpzl3, a novel gene that is conserved among all mammalian species sequenced to date.  The encoded MPZL3 protein is predicted to be a membrane protein likely involved in cell adhesion.  The mutation in the rc mice occurred at a highly conserved amino acid residue, thus likely altering the MPZL3 protein function.  We are currently analyzing the expression pattern of Mpzl3 during normal mouse development as well as in the rc mice, at both the RNA and protein levels.  We are carrying out immunofluorescent staining to determine the cellular and subcellular distribution of MPZL3 protein within the hair follicles.  We are also analyzing the effects of the rc mutation on MPZL3 function in cultured human keratinocytes, the main cell type found in the epidermis of the skin.  We believe these studies will further our understanding of the MPZL3 protein function, and help us elucidate the pathobiology of certain types of alopecia.