Mouse Genome Informatics
hm1
    Serpini2pq/Serpini2pq
involves: C57BL/6J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype

Runted size and acinar cell loss in Serpini2pq/Serpini2pq mice

mortality/aging
• 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

growth/size/body
• homozygotes are on average 1/3 the weight of wild-type
• due to exocrine pancreatic insufficiency

endocrine/exocrine glands
• 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
• 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
• thymocyte numbers are severely reduced, 10-20-fold

hematopoietic system
• 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
• 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
• 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
• 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
• 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
• 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
• reduction in bone marrow cellularity by 21 and 28 days of age
• decrease in early B cell progenitors in the bone marrow
• 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

immune system
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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