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Table 1. Blood cell values of wild-type and TTD mice.
red blood cell count (l 0 I2/L)
hemoglobin (nmlOl)
hematocrite (UL)
mean cell volume (lL)
wild-type mice TTD mice
10.3 8.7
9.4 8.1
0.56 0.47
54.5 54.3
p-value
< 0.01
< 0.01
< 0.01
>0.05
A significant difference of plasma concentration between wild-type and TTD mice
was also found for I-methyl-histidine and phenylalanine (all other amino acid
concentrations, as well as albumin, glucose, creatinin, LDH and urea levels were
normal, see table 2 and data not shown). We determined whether abberant food
uptake or malabsorbtion of food in the intestines could account for starvation in
TTD mice. First, dental abnormalities were excluded. Faeces ofTTD mice appeared
BannaI and even in severely cachectic animals, food was found in stomach and
intestines, indicating that TTD mice fed nomlally. Furthermore, we analysed the
intestines histologically but no gross abnonnalities were found. It must be noted
however that TTD mice suffered more frequently from prolapse of the rectum than
wild-type mice so an intestinal abnonnality camlOt be excluded completely.
To investigate whether malabsorbtion of food occuned in TID mice we analysed
the organic acids of urine because certain changes are typical for intestinal bacterial
degradation when malabsOlption occurs (24]. However, no aberrant organic acids in
urine of TID compared to wild-type mice were detected (data not shown), arguing
against malabsorbtion as the cause of starvation in TTD mice. Further pathology of
TTD mice did not specify abnoffilaIities in other vital organs as liver, kidney or
spleen. In summary, TID mice suffer from progressive failure to thrive due to
starvation, which is likely to be the cause of premature death, but we failed to
identify one major cause of this feature.
Figure 5. Fatty tissue hypoplasia in TTD mice. Photograph of the abdominal cavity of an 18 months
old wild-type (lett) mouse shows excessive fat compared to the TTD iittermate (right).
Premature aging in TTD mice 113