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Phenotypes associated with this allele
Allele Symbol
Allele Name
Allele ID
Bhlha15tm1Skz
targeted mutation 1, Stephen F Konieczny
MGI:2182768
Summary 3 genotypes
Jump to Allelic Composition Genetic Background Genotype ID
hm1
Bhlha15tm1Skz/Bhlha15tm1Skz B6.129S6-Bhlha15tm1Skz MGI:3577891
hm2
Bhlha15tm1Skz/Bhlha15tm1Skz involves: 129S6/SvEvTac MGI:5660614
hm3
Bhlha15tm1Skz/Bhlha15tm1Skz involves: 129S6/SvEvTac * C57BL/6 MGI:5660615


Genotype
MGI:3577891
hm1
Allelic
Composition
Bhlha15tm1Skz/Bhlha15tm1Skz
Genetic
Background
B6.129S6-Bhlha15tm1Skz
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Bhlha15tm1Skz mutation (1 available); any Bhlha15 mutation (15 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
endocrine/exocrine glands
• zymogen granule rare in embryos but become more abundant after birth
• acinar cell disruptions similar to those of the pancreas are seen
• morphology of the chief cells is disrupted
• although initial development of the seminal vesicle is normal, mice exhibit impaired differentiation of cell morphology and function of the secretory epithelium leading to degeneration of the seminal vesicle
• at 2 months of age, mice display abnormal cell morphology in seminal vesicle epithelium, as shown by altered Toluidine blue staining intensity either of the nuclei or cytoplasm
• at high magnification, epithelial secretory cells show reduced ruffling of the luminal border and atypical granule localization
• at 2 months of age, TEM analysis indicates decreased granule size, abnormal (electron dense) granules as well as decreased microvilli and distended ER suggestive of reduced exocytosis ability
• at 12 months of age, mice show progressive deterioration and degeneration of the seminal vesicle epithelium, with numerous abnormal intracellular granules, altered nuclear architecture (indented border and electron dense appearance), and significant accumulations of autophagic bodies

digestive/alimentary system
• zymogen granule rare in embryos but become more abundant after birth
• acinar cell disruptions similar to those of the pancreas are seen
• morphology of the chief cells is disrupted
• glandular cells are more cuboidal than columnar in form

reproductive system
N
• despite alterations in seminal fluid composition, male reproductive function and fertility are normal, as determined by the number of identified copulatory plugs, number of litters generated, and number of offspring per litter
• although initial development of the seminal vesicle is normal, mice exhibit impaired differentiation of cell morphology and function of the secretory epithelium leading to degeneration of the seminal vesicle
• at 2 months of age, mice display abnormal cell morphology in seminal vesicle epithelium, as shown by altered Toluidine blue staining intensity either of the nuclei or cytoplasm
• at high magnification, epithelial secretory cells show reduced ruffling of the luminal border and atypical granule localization
• at 2 months of age, TEM analysis indicates decreased granule size, abnormal (electron dense) granules as well as decreased microvilli and distended ER suggestive of reduced exocytosis ability
• at 12 months of age, mice show progressive deterioration and degeneration of the seminal vesicle epithelium, with numerous abnormal intracellular granules, altered nuclear architecture (indented border and electron dense appearance), and significant accumulations of autophagic bodies
• at 2 months of age, no clear zone between the seminal fluid and epithelial lining is observed, suggesting altered seminal fluid composition and decreased viscosity
• at 10 months of age, seminal fluid shows increased accumulation of 1,4-alpha-D-glucan glucanohydrolase (53 kDa; salivary and hepatic precursor for alpha-amylase), seminal vesicle secretory protein 2 (semenoclotin; 40 kDa), and carcinoembryonic antigen (CEA)-related cell adhesion molecule 10 (CEACAM10; 37 kDa), as shown by mass spectrometry analysis
• conversely, accumulation of seminal vesicle secretory (SVS) proteins IV and V (25 kDa) is reduced relative to wild-type controls




Genotype
MGI:5660614
hm2
Allelic
Composition
Bhlha15tm1Skz/Bhlha15tm1Skz
Genetic
Background
involves: 129S6/SvEvTac
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Bhlha15tm1Skz mutation (1 available); any Bhlha15 mutation (15 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
digestive/alimentary system
• extensive duct cell accumulation
• structural abnormalities of acinar cells
• progressive deterioration of acinar cells until 9-10 months of age, distended acini or ducts and accumulations of non-acinar cell types
• zymogen granules are dispersed throughout acinar cells rather than being apically clustered
• pancreatic tissues are functionally normal in young mice but by 12 months of age there is a loss of enzyme expression

endocrine/exocrine glands
• pancreatic tissues are functionally normal in young mice but by 12 months of age there is a loss of enzyme expression
• increased vascularity of pancreas tissue
• extensive duct cell accumulation
• structural abnormalities of acinar cells
• progressive deterioration of acinar cells until 9-10 months of age, distended acini or ducts and accumulations of non-acinar cell types
• zymogen granules are dispersed throughout acinar cells rather than being apically clustered
• increased levels of connective tissue with age




Genotype
MGI:5660615
hm3
Allelic
Composition
Bhlha15tm1Skz/Bhlha15tm1Skz
Genetic
Background
involves: 129S6/SvEvTac * C57BL/6
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Bhlha15tm1Skz mutation (1 available); any Bhlha15 mutation (15 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
digestive/alimentary system
• intercellular communication among acinar cells is defective

integument
• although lobuloalveolar integrity is normal at early lactation times (L2-L5), late lactating (L15) mammary glands have disrupted lobuloalveolar organization, exhibiting shedding of cells into the alveolus lumen
• E-cadherin and beta-catenin lateral borders are significantly extended as the cells elongate into the acini lumens
• many of the budding cells are binucleated, suggesting that the structural defects negatively influence cytokinesis
• as lactation progresses, cells fail to maintain expression of the gap junction proteins connexin26 and connexin32, leading to the loss of gap junctions
• a lower epithelial cell density is observed during late lactation events (L15-L20) due to increased epithelial cell apoptosis
• late lactating alveolar cells undergo early-stage apoptosis
• late lactating (L15-L20) alveolar cells exhibit precocious activation of the signal transducer and activator of transcription 3 (Stat3) signaling pathway
• late lactating (L15-L20) mammary glands show a significant increase in the number of epithelial apoptotic cells, as shown by TUNEL analysis
• late lactating (L15-L20) mammary glands show a significant increase in the number of epithelial apoptotic cells, as shown by TUNEL analysis
• most apoptotic cells are present in the lumen of individual acini

endocrine/exocrine glands
N
• early lactation (L2-L5) mammary glands express a normal complement of milk proteins (beta-casein, whey acidic protein) and mothers produce sufficient milk to support the normal growth of their offspring
• intercellular communication among acinar cells is defective
• although lobuloalveolar integrity is normal at early lactation times (L2-L5), late lactating (L15) mammary glands have disrupted lobuloalveolar organization, exhibiting shedding of cells into the alveolus lumen
• E-cadherin and beta-catenin lateral borders are significantly extended as the cells elongate into the acini lumens
• many of the budding cells are binucleated, suggesting that the structural defects negatively influence cytokinesis
• as lactation progresses, cells fail to maintain expression of the gap junction proteins connexin26 and connexin32, leading to the loss of gap junctions
• a lower epithelial cell density is observed during late lactation events (L15-L20) due to increased epithelial cell apoptosis
• late lactating alveolar cells undergo early-stage apoptosis
• late lactating (L15-L20) alveolar cells exhibit precocious activation of the signal transducer and activator of transcription 3 (Stat3) signaling pathway
• late lactating (L15-L20) mammary glands show a significant increase in the number of epithelial apoptotic cells, as shown by TUNEL analysis
• late lactating (L15-L20) mammary glands show a significant increase in the number of epithelial apoptotic cells, as shown by TUNEL analysis
• most apoptotic cells are present in the lumen of individual acini





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last database update
09/24/2024
MGI 6.24
The Jackson Laboratory