Analysis Tools
mortality/aging
|
• only very few homozygotes survive beyond 4 weeks and none survive beyond 16 weeks of age
|
|
• heterozygous matings yield ~7.9% of homozygous embryos (versus expected 25%) at E14.5
• only ~5.5% of live homozygous pups are recovered from heterozygous matings
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growth/size/body
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• significant reduction in body weight after P4
• however, feeding is normal
|
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• although normal at birth, mice exhibit growth retardation by the end of the first postnatal week
|
reproductive system
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• absence of ovarian corpora lutea
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infertility
(
J:211308
)
|
• mice are sterile
|
integument
waved hair
(
J:211308
)
|
• curly hair
|
|
• epidermal hyperkeratosis
|
behavior/neurological
paraparesis
(
J:211308
)
|
• hind limb weakness
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muscle
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• thin skeletal muscle bundles
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renal/urinary system
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• progressive hydronephrosis
|
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• vacuolated renal tubular cells
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immune system
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• numerous pyknotic and karyorrhectic nuclei in the thymus
|
|
• very thin thymus cortical layer
|
|
• effacement of the thymus corticomedullary junction
|
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• disorganized thymus medulla
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small thymus
(
J:211308
)
|
• markedly smaller thymus
|
|
• ~10-fold reduction in thymus cellularity
|
|
• marked reduction in thymocyte numbers
|
|
• significant decrease in DN2 thymocyte number at 3-6 weeks of age
• however, DN1 thymocyte number and distribution of DN1a-e subsets are normal
|
|
• significant decrease in DN3 thymocyte number at 3-6 weeks of age
|
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• significant decrease in DN4 thymocyte number at 3-6 weeks of age
|
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• marked reduction of AKT phosphorylation in thymocytes
|
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• increased numbers of CD3+ cells that co-stain for activated caspase 3
• increased % of annexin V+ apoptotic thymocytes at 3-6 weeks of age
|
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• increased numbers of TUNEL+ apoptotic cells in the thymus
|
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• modest impairment in B cell development
• however, splenic B cells proliferate normally to anti-IgM, anti-CD40 and LPS, and antibody response to type I T-independent (TI) antigen (TNP-LPS) and to type II TI antigen (TNP-Ficoll) is normal, indicating intact B cell function
|
|
• modest decrease in the % of CD43-B220lowIgM+ immature B cells in the bone marrow
|
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• modest decrease in the % of transitional B cells in spleen
|
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• modest increase in the % of CD43+B220lowIgM- pro-B cells in the bone marrow
|
|
• severe cell-intrinsic block in early thymocyte development
|
|
• analysis of TCR-Vbeta CDR3 diversity in splenic T cells at 6 weeks of age revealed partial restriction of the T cell repertoire, as shown by skewed distribution for some (~25%), but not all, of the TCR-Vbeta families analyzed
|
|
• significant decrease in double-negative thymocytes at 3 weeks of age
|
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• drastic decrease in double-positive thymocytes at 3 weeks of age
|
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• modest decrease in the % of B220hi IgMhi recirculating B cells in the bone marrow
• ~4-fold reduction in the number of B220+ cells in spleen
• however, % of splenic B220+AnnexinV+ cells is normal
• numbers and subset distribution of peritoneal B220+ B cells are normal
|
|
• modest decrease in the % of marginal zone B cells in spleen
• however, % of splenic follicular B cells is normal
|
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• modest decrease in the % of CD43-B220lowIgM- pre-B cells in the bone marrow
|
|
• significant increase in the % of CD4+ FOXP3+ regulatory T cells in the thymus
|
|
• significant reduction in the number of T cells in spleen
• however, the CD4/CD8 ratio and % of splenic CD3+ Annexin V+ cells are normal
|
|
• significant decrease in single-positive thymocytes at 3 weeks of age
|
|
• significant decrease in single-positive thymocytes at 3 weeks of age
|
small spleen
(
J:211308
)
|
• small spleens with well-preserved architecture
|
|
• increased serum IgG2a levels at 4-6 weeks of age
• however, serum levels of IgM, IgA, and IgG1, IgG2b and IgG3 isotypes are normal
|
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• impaired peripheral T cell function
|
|
• marked decrease in % of BrdU+ thymocytes at 3-6 weeks of age
• impaired proliferation of splenic T cells to immobilized anti-CD3, not increased by the addition of anti-CD28 mAb or IL-2
|
endocrine/exocrine glands
|
• numerous pyknotic and karyorrhectic nuclei in the thymus
|
|
• very thin thymus cortical layer
|
|
• effacement of the thymus corticomedullary junction
|
|
• disorganized thymus medulla
|
small thymus
(
J:211308
)
|
• markedly smaller thymus
|
|
• ~10-fold reduction in thymus cellularity
|
|
• marked reduction in thymocyte numbers
|
|
• significant decrease in DN2 thymocyte number at 3-6 weeks of age
• however, DN1 thymocyte number and distribution of DN1a-e subsets are normal
|
|
• significant decrease in DN3 thymocyte number at 3-6 weeks of age
|
|
• significant decrease in DN4 thymocyte number at 3-6 weeks of age
|
|
• absence of ovarian corpora lutea
|
|
• marked reduction of AKT phosphorylation in thymocytes
|
|
• increased numbers of CD3+ cells that co-stain for activated caspase 3
• increased % of annexin V+ apoptotic thymocytes at 3-6 weeks of age
|
|
• increased numbers of TUNEL+ apoptotic cells in the thymus
|
hematopoietic system
|
• numerous pyknotic and karyorrhectic nuclei in the thymus
|
|
• very thin thymus cortical layer
|
|
• effacement of the thymus corticomedullary junction
|
|
• disorganized thymus medulla
|
small thymus
(
J:211308
)
|
• markedly smaller thymus
|
|
• ~10-fold reduction in thymus cellularity
|
|
• marked reduction in thymocyte numbers
|
|
• significant decrease in DN2 thymocyte number at 3-6 weeks of age
• however, DN1 thymocyte number and distribution of DN1a-e subsets are normal
|
|
• significant decrease in DN3 thymocyte number at 3-6 weeks of age
|
|
• significant decrease in DN4 thymocyte number at 3-6 weeks of age
|
|
• marked reduction of AKT phosphorylation in thymocytes
|
|
• increased numbers of CD3+ cells that co-stain for activated caspase 3
• increased % of annexin V+ apoptotic thymocytes at 3-6 weeks of age
|
|
• increased numbers of TUNEL+ apoptotic cells in the thymus
|
|
• modest impairment in B cell development
• however, splenic B cells proliferate normally to anti-IgM, anti-CD40 and LPS, and antibody response to type I T-independent (TI) antigen (TNP-LPS) and to type II TI antigen (TNP-Ficoll) is normal, indicating intact B cell function
|
|
• modest decrease in the % of CD43-B220lowIgM+ immature B cells in the bone marrow
|
|
• modest decrease in the % of transitional B cells in spleen
|
|
• modest increase in the % of CD43+B220lowIgM- pro-B cells in the bone marrow
|
|
• severe cell-intrinsic block in early thymocyte development
|
|
• analysis of TCR-Vbeta CDR3 diversity in splenic T cells at 6 weeks of age revealed partial restriction of the T cell repertoire, as shown by skewed distribution for some (~25%), but not all, of the TCR-Vbeta families analyzed
|
|
• modest decrease in the % of B220hi IgMhi recirculating B cells in the bone marrow
• ~4-fold reduction in the number of B220+ cells in spleen
• however, % of splenic B220+AnnexinV+ cells is normal
• numbers and subset distribution of peritoneal B220+ B cells are normal
|
|
• modest decrease in the % of marginal zone B cells in spleen
• however, % of splenic follicular B cells is normal
|
|
• modest decrease in the % of CD43-B220lowIgM- pre-B cells in the bone marrow
|
|
• significant increase in the % of CD4+ FOXP3+ regulatory T cells in the thymus
|
|
• significant reduction in the number of T cells in spleen
• however, the CD4/CD8 ratio and % of splenic CD3+ Annexin V+ cells are normal
|
|
• significant decrease in double-negative thymocytes at 3 weeks of age
|
|
• drastic decrease in double-positive thymocytes at 3 weeks of age
|
|
• significant decrease in single-positive thymocytes at 3 weeks of age
|
|
• significant decrease in single-positive thymocytes at 3 weeks of age
|
small spleen
(
J:211308
)
|
• small spleens with well-preserved architecture
|
|
• increased serum IgG2a levels at 4-6 weeks of age
• however, serum levels of IgM, IgA, and IgG1, IgG2b and IgG3 isotypes are normal
|
|
• impaired peripheral T cell function
|
|
• marked decrease in % of BrdU+ thymocytes at 3-6 weeks of age
• impaired proliferation of splenic T cells to immobilized anti-CD3, not increased by the addition of anti-CD28 mAb or IL-2
|
cellular
|
• increased numbers of CD3+ cells that co-stain for activated caspase 3
• increased % of annexin V+ apoptotic thymocytes at 3-6 weeks of age
|
|
• increased numbers of TUNEL+ apoptotic cells in the thymus
|
|
• marked decrease in % of BrdU+ thymocytes at 3-6 weeks of age
• impaired proliferation of splenic T cells to immobilized anti-CD3, not increased by the addition of anti-CD28 mAb or IL-2
|
homeostasis/metabolism
| N |
• serum levels of TNF and cortisol are normal
|
