A quantitative trait locus on chr.4 regulates thymic involution.
The mechanisms underlying age-associated thymic involution are unknown. In mice, thymic involution shows mouse strain-dependent genetic variation. Identification of the underlying genes would provide mechanistic insight into this elusive process. We previously showed that responsiveness of hematopoietic stem and progenitor cells (HSPCs) to transforming growth factor-beta 2, a positive regulator of HSPC proliferation, is regulated by a quantitative trait locus (QTL) on chr. 4, Tb2r1. Interestingly, Tgfb2(+/-) mice have delayed thymic involution. Therefore, we tested the hypothesis that a QTL on chr. 4 might regulate thymic involution. Aged, but not young, B6.D2-chr.4 congenic mice, where the telomeric region of chr. 4 was introgressed from DBA/2 to C57BL/6 mice, had larger thymi, and better maintenance of early thymic precursors than C57BL/6 control mice. These observations unequivocally demonstrate that the telomeric region of chr. 4 contains a QTL, Ti1 (thymic involution 1) that regulates thymic involution, and suggest the possibility that Ti1 may be identical to Tb2r1.
Kumar
Ritu
R
Department of Gene and Cell Medicine, Mount Sinai of School of Medicine, Gustave L. Levy Place, PO Box 1496, New York, NY 10029, USA.
Avagyan
Serine
S
Snoeck
Hans-Willem
HW
D000375:Aging / Q000502:physiology*; D000818:Animals; D033481:Chromosomes, Mammalian / Q000235:genetics*; D051379:Mice; D020297:Mice, Congenic; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D040641:Quantitative Trait Loci / Q000502:physiology*; D013234:Stem Cells / Q000166:cytology; D013950:Thymus Gland / Q000033:anatomy & histology / Q000166:cytology / Q000502:physiology*; D013997:Time Factors; D053781:Transforming Growth Factor beta2 / Q000235:genetics / Q000502:physiology*
D053781:Transforming Growth Factor beta2