Longitudinal assessment of immunologic abnormalities of mice with the autosomal recessive mutation, "wasted"

Mice homozygous for the autosomal recessive mutation wasted (wst/wst) undergo a progressive wasting beginning at the third week of postnatal life, when body weight declines in the mutants. The wst/wst mice do not survive past 30 days of age. The present report describes histologic and functional abnormalities in a longitudinal analysis (17 to 29 days postpartum) of wst/wst mice. In addition to a marked age-dependent decline in wst/wst body weight as well as spleen and thymus wet weight to body weight ratios, we have observed a significant decline in spleen and thymus cell number in these organs, compared with phenotypically normal (+/+ or +/wst) littermates. Histologic analysis of the wst/wst thymus revealed marked cortical pyknosis at 23 days of age and significant cortical depletion by 26 days postpartum. The wst/wst spleen at 23 days of age and later was characterized by a marked reduction in the content of red pulp. Lymphoproliferative responsiveness to Con A was markedly altered in the wst/wst thymus and spleen, in an age-dependent fashion, compared with normal littermates. The wst/wst spleen LPS responsiveness was also markedly altered in an age-dependent fashion. Hypotheses are presented concerning the possible site(s) of gene action in the wst/wst mutant which may mediate the observed morphologic and functional abnormalities.