International Mammalian Genome Society

The 16th International Mouse Genome Conference (2002)


F Iraqi
International Livestock Research Institute (ILRI)

1) Nakamura Y, 2) Tsuchiya Y, 3) Naessens J, 3) Gibson J
1) Japan International Research Center for Agricultural Sciences, 2) National Institute of Animal Health (Japan), 3) International Livestock Research Institute

Susceptible A/J mice develop higher parasitemia, but less severe anemia than resistant C57BL/6 mice following Trypanosoma congolense infection.  Parasitemias in A/J are even higher than in TNF-a-deficient C57BL/6 mice, which are also very susceptible.  These observations suggest that A/J mice are capable of suppressing protective responses having detrimental effects to the host, such as anemia.  Glucocorticoids play a central role in suppression of inflammatory and immune responses.  Therefore, glucocorticoid responses were compared between A/J, wild-type and TNF-a-deficient C57BL/6 mice up to day 17 following infection.  Serum corticosterone was determined by radioimmunoassay.  The expression level of Cyp21a, which is located within the major trypanosome resistance QTL, Tir1, and encodes an enzyme involved in corticosterone synthesis, was monitored by RT-PCR in total RNA extracted from adrenal glands.  Corticosterone concentrations in wild-type and TNF-a-deficient C57BL/6 remained low, except for a transient slight increase at day 7.  However, by day 4 corticosterone increased in A/J to higher levels than in C57BL/6, and thereafter gradually returned to the pre-infection levels.  A lower expression of Cyp21a-mRNA was observed in pre-infection samples from A/J than from C57BL/6.  Following infection, the expression increased in A/J to levels detected in C57BL/6.  In C57BL/6, the expression did not significantly change during infection.  This study described higher glucocorticoid responses in A/J than in C57BL/6, but no differences between wild type and TNF-a-deficient C57BL/6.  The results conform with the hypothesis that a higher activation of the glucocorticoid pathway in A/J mice results in higher parasitemia and less severe anemia.

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