Dr Rebecca M. Porter
My work centres on the study of the hair follicle with two main areas of interest. The first is into mouse mutations with hair-loss phenotypes and the second is a human mapping project to find the gene underlying a familial case of Trichoepithelioma.
THE HAIR FOLLICLE
The hair follicle is an amazingly complex mini-organ that consists of many epithelial layers composing and surrounding the hair shaft. The outer root sheath is the outermost epithelial layer of the hair follicle that is continuous with the epidermis. Inside this layer is the inner root sheath that actually consists of three different cell lineages; the Henle's layer, Huxley's layer and cuticle. The hair shaft is also composed of three layers; the cuticle, cortex and medulla. Finally one very thin layer also exists between the inner root sheath and outer root sheath. This is known as the companion layer. As well as these concentric epithelial rings there is an additional epithelial lineage that forms the sebaceous gland. This gland is responsible for the production of a specialised mixture of lipids (sebum) that is released into a duct into the infundibulum (upper neck of the follicle) of the hair follicle lubricating the emerging hair shaft and the epidermis.
KERATINS OF THE HAIR FOLLICLE
My interest in the hair follicle began with the study of hair follicle keratin expression. Keratins are important structural proteins of the cytoskeleton that are expressed in pairs of one type I and one type II keratin. The co-expression of equi-molar quantities of these two classes of keratin is paramount for the formation of the intermediate filaments of epithelial cells. There are over 40 different keratins expressed in a tissue and differentiation specific manner but it wasn't until the sequencing of the human and mouse genomes that the inner root sheath keratins were identified.
DEFOLLICULATED: A MOUSE HAIR LOSS MUTATION
More recently my interest in the hair follicle has expanded to other areas. This was stimulated by a mouse mutation that occurred spontaneously in Bonn causing a hair-loss phenotype. Histological examination of the skin of these mice indicated that they have a defect in the differentiation of the sebaceous gland. They also have a defective hair growth cycle. Normally the hair follicle undergoes a cycle of growth, regression and rest where the follicle dramatically changes it morphology.
Fig3: Diagram of the hair cycle
In Defolliculated the regression phase starts but is incomplete so that in the subsequent growth phase, the hair follicle grows abnormally long. Ultimately this aberrant growth is halted by the complete elimination of all the follicles in the pelage (coat) leaving the mouse completely naked apart from the vibrissae and some snout hairs.
Defolliculated has a mutation in a gene called gasdermin 3, expressed in the upper epidermis, mature sebaceous gland cells and the differentiating inner root sheath and hair shaft. In addition to defolliculated there are a number of other mouse mutants on chromosome 11. Of these I am also investigating finnegan (in collaboration with Pat Nolan) that was generated by ENU mutagenesis at Harwell, UK and has an identical phenotype to defolliculated and carries a mutation in the same gene.
Two other mouse mutants I am interested in, alopecia 1 and alopecia 2, are also mapped to chromosome 11 and were also generated by ENU mutagenesis at The Centre for Modeling Human Disease in Toronto.
There are a number of hair follicle derived tumours including trichoepithelioma, trichofolliculoma, sebaceous adenoma, pilomatricoma, tricholemmona and even basal cell carcinoma, the commonest skin tumour, is thought to be hair follicle derived.
Trichoepithelioma and basal cell carcinoma, although usually clinically distinct, are very similar histologically and some cases have been difficult to diagnose. It has therefore been hypothesised that they may have common origins. We are addressing this possibility by doing genetic linkage analysis of an Italian pedigree with familial trichoepithelioma.
Publications on the hair follicle:
Hair follicle keratin papers:
Porter RM, Corden LD, Lunny DP, Smith FJD, Lane EB,McLean WHI: Keratin K6irs is specific to the inner root sheath of hair follicles in mice and humans. Brit J Dermatol 145: 558-568, 2001
Peters T, Sedlmeier R, Büssow H, et al: Alopecia in a novel mouse model RCO3 is caused by mK6irs deficiency. J Invest Dermatol 121: 674-680, 2003
Porter RM, Gandhi M, Wilson NJ, McLean WHI,Lane EB: Functional analysis of keratin components in the mouse hair follicle inner root sheath. Brit J Dermatol 150: 195-204, 2004
Porter RM, Jahoda CAB, Lunny DP, et al: Defolliculated (Dfl): A dominant mutation leading to poor sebaceous gland differentiation and total elimination of pelage follicles. J Invest Dermatol 119: 32-37, 2002
Lunny DP, Weed E, Nolan PM, Marquardt A, Augustin M,Porter RM: Mutations in gasdermin 3, cause aberrant differentiation of the hair follicle and sebaceous gland. J Invest Dermatol In Press:
Other hair papers:
Jahoda CAB, Kljuic A, O'Shaughnessy R, et al: The lanceolate hair rat phenotype results from a missense mutation in a calcium coordinating site of the desmoglein 4 gene. Genomics, 83: 747-756, 2004
Porter RM: Mouse models for human hair loss disorders. J Anat 202: 127-133, 2003
Wood GA, Flenniken A, Osborne L, et al: Two mouse models of autoimmune alopecia with differing morphologies but similar clinical progression. Exp. Dermatol. In Press.