Office: Copernicus 204
Lab: Copernicus 429 (Animal Suite)
- BMS 102 - Introduction to Biomolecular Sciences
- BMS 103 - Introduction to Biomolecular Sciences Lab
- BMS 201 - Principles of Cell and Molecular Biology
- BMS 306 - Principles of Genetics
- BMS 570 - Advanced Genetics
My research interests concern the genetic analysis of development in mammals, using mice and rats
as model mammalian systems. With the long-term goal of gaining access to the molecular biology
underlying interesting mutant phenotypes, my work prior to my appointment at CCSU produced a number of
high-resolution genetic maps including genomic regions on mouse Chromosomes 7, 10, 17 and the Y
Chromosome. At CCSU, my laboratory has investigated a novel mutation in rats (designated
that causes recessive alopecia (Moemeka et al., J. Heredity 89, 257-260; Hall et al., J. Heredity 91,
345-347; Chrissluis et al., 2002, Molecular Genetics and Metabolism, 76, 335-339), and we have made
progress mapping the X-linked histoincompatibility locus (Alner et al., Immunogenetics 55, 87-94).
We are currently pursuing three different projects:
- We are investigating the molecular genetic basis of a pleiotropic developmental mutation in the
mouse, designated mshi. This mutation controls recessive male sterility, and loss of an unusual new
type of histocompatibility locus that is detected in vivo by helper T cells. We have mapped this
mutation to mouse Chr 10 (Turner et al., Genomics 39, 1-7; Rule et al., Mammalian Genome 10,
447-450), and have made progress characterizing both the histocompatibility (Hildebrandt et al.,
Immunogenetics 49, 666-672) and reproductive aspects of the mutant phenotype. We have also
investigated the occurrence of programmed cell death (apoptosis) in mutant gonads, vs. wild type
(in collaboration with James Mulrooney, CCSU). We have recently discovered that
Mtap7 is the gene
disrupted by the mshi mutation (Magnan et al., Molecular Genetics and Metabolism 97, 155-162). Further
studies of the Mtap7mshi allele will be supported by an AREA grant through 2010.
- Another project, the mapping of the Charles River “hairless” mutation, was started in Fall, 2001
(Ahearn et al., J. Heredity 93, 210-213). This work suggested Fgfr2 as a possible gene candidate for
the Charles River “hairless” mutation, which we also showed is an allele of rat
fuzzy and a likely orthologue of mouse frizzy. Our research has created a high-resolution map for the mouse
(Paul et al., Experimental Dermatology, 17, 640-644), which has facilitated the identification of the
single base-pair change in the Prss8 gene that causes the mutant fr phenotype (Spacek et al.,
Experimental Dermatology, in press). We have also found a 12-basepair deletion in the
Prss8 gene in
hairless rats, and expect to find a Prss8 defect in the fuzzy rat as well. An AREA grant will support
this work through 2010.
- We are initiating a new positional cloning program, which will aim to identify the gene mutated
in a set of 6 mutants with mutations that affect hair development. Analysis of large backcrosses
segregating for wooly (wly) and juvenile alopecia (jal) are currently in progress.
Publications (CCSU student authors are underlined):
- D.V. Spacek, A.F. Perez, K.M. Ferranti, L.K.-L Wu, D.M. Moy, D.R. Magnan & T.R. King. The mouse
frizzy (fr) and rat “hairless” (frCR) mutations are natural variants of protease serine S1 family
member 8 (Prss8). In Press at Experimental Dermatology (Dec, 2009)
- D.R. Magnan, D.V. Spacek, N. Ye, Y.-C. Lu & T.R. King (2009) The male sterility and histoincompatibility (mshi) mutation in mice is a natural variant of microtubule-associated protein 7
(Mtap7). Molecular Genetics and Metabolism 97, 155-162.
E.L. Paul, R. Badal, D.S. Thompson, D.R. Magnan, F.M. Soucy, I.M. Khan, R.A. Haughton & T.R. King
(2008). The mouse frizzy mutation (fr) maps between D7Csu5 and
D7Mit165. Experimental Dermatology 17,
Alner, K.A., Loman, J., Hall, E.H., Mutcherson II, R.J. & King, T.R. (2003)
An X-encoded alloantigenicity between BALB/c and C57BL/6 strains of mice. Immunogenetics 55, 87-94.
R.R. Chrissluis, T. Stoklasek, J. Loman, A. Guariglia & T.R. King
(2002).The rat shorn mutation (shn) maps between D7Got143 and D7Rat94. Molecular
Genetics and Metabolism 76, 335-339.
K. Ahearn, G. Akkouris, P.R. Berry, R. R. Chrisslius, I. Crooks,
A.K. Dull, S. Grable, J. Jeruzal, J. Lanza, C. Lavoie, R. A. Maloney,
M. Pitruzzello, R. Sharma, T.A. Stoklasek, J. Tweeddale & T.R. King. The
Charles River “hairless” rat mutation: Maps to Chromosome 1, allelic with fuzzy,
and a likely orthologue of mouse frizzy. Journal of Heredity 93, 210-213.
E.H. Hall, J.A. Lathrop, B. Medina, R.J.
Mutcherson II & T.R. King (2000) The hypotrichosis-generating shorn (shn)
mutation maps to distal Chromosome 7 in the Norway rat. Journal of Heredity
M. C. Rule, R. J. Mutcherson II, A. D. Foss, T.
K.-X. Nguyen, K. A. Myrie & T. R. King (1999) Mouse male
sterility and histocompatibility (mshi) maps between the D10Mit51/168/212
cluster and D10Mit213. Mammalian Genome 10, 447-450.
A. L. Hildebrandt, A. M. Cantwell, M.C. Rule &
T.R. King (1999) The H-mshi antigen is conserved between standard BALB/cBy,
C57BL/6J, and wild-derived CAST/Ei and SPRET/Ei inbred strains of mice.
Immunogenetics 49, 666-672.
A. N. Moemeka, A. L. Hildebrandt, P. Radaskiewicz
& T. R. King (1998) Shorn (shn): A new mutation causing hypotrichosis in
the Norway rat. Journal of Heredity89,257-260.
J. P. Turner, J. E. Carpentino, A. M. Cantwell, A.
L. Hildebrandt, K. A. Myrie & T. R. King (1997) Molecular genetic mapping of the
mouse male sterility and histoincompatibility (mshi) mutation on proximal Chromosome
10.Genomics 39, 1-7.
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December 15, 2009