TABLE 3.
Histopathological assessment of Tg mice expressing different Nef alleles
| Diseased organ | No. of animals with disease/total number of animalsa
|
|||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| AD-93
|
032an
|
039nm
|
JR-CSF
|
YU10x
|
SF2
|
NL4-3T71R
|
||||||||
| F115820 (M) | F115817 (L) | F95582 (L-M) | F95581 (L-M) | F75581 (M) | F51444 (M) | F104996 (L) | F104995 (H) | F92754 (L) | F92751 (H) | F92748 (L) | F92749 (L) | F101376 (L) | F101371 (L) | |
| Thymusb | 9/12 | 2/7 | 6/7 | 1/9 | 13/13 | 5/9 | 2/12 | 8/14 | 2/17 | 0/7 | 7/10 | 0/7 | 3/7 | 0/10 |
| LNc | 11/13 | 8/9 | 6/9 | 4/11 | 7/11 | 5/8 | 4/12 | 4/14 | 7/17 | 3/13 | 2/7 | 3/11 | 4/8 | 7/14 |
| Kidneyd | 0/14 | 0/9 | 11/11 | 4/11 | 13/13 | 9/9 | 5/12 | 2/14 | 1/18f | 0/13 | 5/13g | 3/14g | 13/13 | 8/15 |
| Lunge | 0/14 | 0/9 | 0/11 | 2/11 | 3/13 | 2/9 | 2/12 | 0/14 | 0/18 | 0/13 | 0/13 | 2/14g | 0/13 | 2/15 |
Number of animals with disease over total number of animals studied for the two founders of each Tg line showing the most severe phenotype. Non-Tg mice (n = 86) showed none of these phenotypes. The levels of RNA expression in the thymus are provided in parentheses. L, low; M, medium; H, high. Medium expression is comparable to that of NefNL4-3(WT) (F27367).
Atrophy and disorganization.
Diseases include follicle hyperplasia, fragmentation, involution, and relative enlarged paracortex with lymphocytopenia. For the 032an, 039nm, JR-CSF, and NL4-3T71R Nef alleles, the predominant change is depletion of lymphocytes throughout the LN.
Different degrees of glomerulopathy include focal segmental glomerulosclerosis and tubulointerstitial nephritis with microcystic dilation.
Lymphocytic interstitial pneumonitis.
Despite high expression levels in NefYU10x (F92751)-expressing mice, kidney disease was mild.
The low penetrance of disease in NefSF2 Tg mice is likely to be related to the low levels of expression in both founder lines relative to those of the NefNL4-3(WT) Tg mice.