Analysis Tools
mortality/aging
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• typically live 2-7 months; lifespan increases when mutants are housed in sterile cages with acidified water or when mutants are supplemented with pancreatic enzymes
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growth/size/body
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• homozygotes are on average 1/3 the weight of wild-type
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• due to exocrine pancreatic insufficiency
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endocrine/exocrine glands
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• loss of acinar cells, due to progressive apoptosis, in the exocrine pancreas between 1 and 3 weeks of age such that by 3 weeks of age, mutants have only about 1/2 the number of pancreatic acinar cells, despite normal appearance of ductal and endocrine islet cells
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• acinar cells exhibit a reduction in size and number of dense zymogen granules in the cytoplasm and a lack of dense material within the ductal network
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• pancreatic insufficiency is characterized by loss of pancreatic acinar cells resulting in mice that are unable to absorb nutrients from the diet, stunting growth and giving rise to immunological anomalies
• pancreatic enzyme diet supplementation or BAC transgene rescue restores size, weight, viability and immune cell numbers
|
small thymus
(
J:115744
)
|
• thymus is about 4-fold smaller than in wild-type at 8 weeks of age
• despite the reduction in thymic size, thymocyte profile is normal, with cells progressing from the most immature double negative cells to double positive and single-positive mature cells with no block at any stage; thymic development is not blocked
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• reduction in thymic cellularity by 21 and 28 days of age
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• thymocyte numbers are severely reduced, 10-20-fold
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hematopoietic system
small thymus
(
J:115744
)
|
• thymus is about 4-fold smaller than in wild-type at 8 weeks of age
• despite the reduction in thymic size, thymocyte profile is normal, with cells progressing from the most immature double negative cells to double positive and single-positive mature cells with no block at any stage; thymic development is not blocked
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• reduction in thymic cellularity by 21 and 28 days of age
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• within the CD43+ fraction, pro-B cells express lower levels of CD24, demonstrating that block occurs between the pre-proB and early pro-B cell stage
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• reduction in bone marrow cellularity by 21 and 28 days of age
• decrease in early B cell progenitors in the bone marrow
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• spleens at 3-4 weeks of age show a reduction in lymphoctye numbers
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• B cell numbers are reduced more than 10-fold in spleens at 3-4 weeks of age
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• in the spleen, reduced numbers of the most immature population of B cells (IgM+IgD-) is seen
• expression of IgM on immature cells is lower
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• decrease in mature T cells
• T cell numbers are reduced about 5-fold in the spleen at 3-4 weeks of age
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• thymocyte numbers are severely reduced, 10-20-fold
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• compared to wild-type, pre-B cells manifest a higher percentage of B220+IgM-CD43+ cells, indicating a partial block in B cell development prior to the pre-B cell stage; block becomes more apparent as mutants age
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small spleen
(
J:115744
)
|
• spleen is about 4-fold smaller than in wild-type at 8 weeks of age
|
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• reduction in splenic cellularity by 21 and 28 days of age
• spleens at 3-4 weeks of age show a reduction in lymphocyte numbers, with T cell numbers reduced about 5-fold and B cell numbers reduced more than 10-fold
|
immune system
small thymus
(
J:115744
)
|
• thymus is about 4-fold smaller than in wild-type at 8 weeks of age
• despite the reduction in thymic size, thymocyte profile is normal, with cells progressing from the most immature double negative cells to double positive and single-positive mature cells with no block at any stage; thymic development is not blocked
|
|
• reduction in thymic cellularity by 21 and 28 days of age
|
|
• within the CD43+ fraction, pro-B cells express lower levels of CD24, demonstrating that block occurs between the pre-proB and early pro-B cell stage
|
|
• spleens at 3-4 weeks of age show a reduction in lymphoctye numbers
|
|
• B cell numbers are reduced more than 10-fold in spleens at 3-4 weeks of age
|
|
• expression of IgM on immature cells is lower
• in the spleen, reduced numbers of the most immature population of B cells (IgM+IgD-) is seen
|
|
• decrease in mature T cells
• T cell numbers are reduced about 5-fold in the spleen at 3-4 weeks of age
|
|
• thymocyte numbers are severely reduced, 10-20-fold
|
|
• compared to wild-type, pre-B cells manifest a higher percentage of B220+IgM-CD43+ cells, indicating a partial block in B cell development prior to the pre-B cell stage; block becomes more apparent as mutants age
|
small spleen
(
J:115744
)
|
• spleen is about 4-fold smaller than in wild-type at 8 weeks of age
|
|
• reduction in splenic cellularity by 21 and 28 days of age
• spleens at 3-4 weeks of age show a reduction in lymphocyte numbers, with T cell numbers reduced about 5-fold and B cell numbers reduced more than 10-fold
|
digestive/alimentary system
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• loss of acinar cells, due to progressive apoptosis, in the exocrine pancreas between 1 and 3 weeks of age such that by 3 weeks of age, mutants have only about 1/2 the number of pancreatic acinar cells, despite normal appearance of ductal and endocrine islet cells
|
|
• acinar cells exhibit a reduction in size and number of dense zymogen granules in the cytoplasm and a lack of dense material within the ductal network
|
|
• pancreatic insufficiency is characterized by loss of pancreatic acinar cells resulting in mice that are unable to absorb nutrients from the diet, stunting growth and giving rise to immunological anomalies
• pancreatic enzyme diet supplementation or BAC transgene rescue restores size, weight, viability and immune cell numbers
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| Shwachman-Diamond syndrome | DOID:0060479 |
OMIM:260400 |
J:115744 | |
