The tight skin (Tsk) mutation in the mouse, a model for human fibrotic diseases, is tightly linked to the beta 2-microglobulin (B2m) gene on chromosome 2.
The Tsk mutation in the mouse is characterized by the excessive accumulation of collagen in skin and various internal organs, including the heart and lungs. These connective tissue abnormalities are similar to those present in human systemic sclerosis or scleroderma. The Tsk mutation provides an opportunity to investigate, at the molecular level, the pathogenesis of tissue fibrosis. As a first step to cloning the Tsk gene, we report the localization of the Tsk mutation with respect to known molecular markers on mouse chromosome 2. N2 progeny carrying the Tsk mutation were obtained from an intersubspecific backcross of [(C57BL/6-pa +/+ Tsk x Mus castaneus)F1 x M. castaneus] mice. Genomic DNA from each N2 mouse was subjected to Southern and PCR analyses to identify restriction fragment length polymorphisms and simple sequence length polymorphisms, respectively. Our results refine the location of Tsk to a 3-cM region, eliminate several genes from consideration as the Tsk mutation, identify molecular probes tightly linked with Tsk, and suggest candidate genes responsible for the Tsk phenotype.
Siracusa
L D
LD
Department of Microbiology and Immunology, Jefferson Cancer Institute, Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania 19107-5541.
Christner
P
P
McGrath
R
R
Mowers
S D
SD
Nelson
K K
KK
Jimenez
S A
SA
D000818:Animals; D002874:Chromosome Mapping; D003433:Crosses, Genetic; D004195:Disease Models, Animal; D005260:Female; D008040:Genetic Linkage; D005819:Genetic Markers; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D009115:Muridae; D009154:Mutation; D012150:Polymorphism, Restriction Fragment Length; D012594:Scleroderma, Localized / Q000235:genetics; D012595:Scleroderma, Systemic / Q000235:genetics; D012871:Skin Diseases / Q000235:genetics*; D001613:beta 2-Microglobulin / Q000235:genetics*
D005819:Genetic Markers; D001613:beta 2-Microglobulin