Research Interests
Mouse pigmentation has been studied as a model genetic system since the early 1900’s when investigators used mouse coat colour to test whether Mendel’s laws apply to mammals. Many of the biochemical pathways involved in pigment synthesis and transport are shared with other biological processes and mutations in genes that affect pigmentation frequently have pleiotropic effects. Research in the Gunn lab is currently primarily focused on the study of Attractin and Mahogunin signaling. Mice with mutations in the Attracti1n (Atrn1; formerly named mahogany) and Mahogunin ring finger 1 (Mgrn1; formerly named mahoganoid) genes have dark coats, due to a role in the Agouti-melanocortin signaling pathway that regulates whether melanocytes produce black or yellow pigment. In addition, loss of Atrn in mice, rats and hamsters, or Mgrn1 in mice, results in progressive adult-onset neurodegeneration. In most Attractin mutant mice, neurodegeneration is associated with hyperactivity and decreased body weight. Loss of Mgrn1 also leads to embryonic patterning and congenital heart defects.
We are using genetic, molecular, biochemical and proteomics approaches to identify additional components of the Attractin and Mahogunin signaling pathway(s) and elucidate the molecular mechanism(s) of spongy degeneration and embryonic patterning defects in these mutant animals.
Histological section of thalamus from
a Histological section from
unaffected mouse.
5.5-month old female Atrn1pst112 mutant
mouse showing severe spongiform
degeneration.
We also collaborate with Dr. Sydney Moïse
to study and identify the genetic factors that underlie predisposition to
ventricular arrhythmias and sudden death in dogs (German shepherds).