Phenotypes associated with this allele

• Allele Symbol: Bhlha15^{tm3(cre/ERT2)Skz}
• Allele Name: targeted mutation 3, Stephen F Konieczny
• Allele ID: MGI:3821734
• Summary: 4 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Bhlha15^tm3(cre/ERT2)Skz/Bhlha15^tm3(cre/ERT2)Skz	involves: 129S1/Sv * 129X1/SvJ * C57BL/6	MGI:5828129
cn2	Kras^tm4Tyj/Kras^tm4Tyj Bhlha15^tm3(cre/ERT2)Skz/Bhlha15^+	involves: 129S1/Sv * 129S4/SvJae * 129X1/SvJ	MGI:3821739
cn3	Bhlha15^tm3(cre/ERT2)Skz/Bhlha15^tm3(cre/ERT2)Skz Tg(CAG-Bhlha15)1Skz/0	involves: 129S1/Sv * 129X1/SvJ * C57BL/6	MGI:5827856
cn4	Bhlha15^tm3(cre/ERT2)Skz/? Gt(ROSA)26Sor^tm4(ACTB-tdTomato,-EGFP)Luo/? Trip11^tm1.1Psmi/Trip11^tm1.2Psmi	involves: 129/Sv * C57BL/6	MGI:6154165

Genotype
MGI:5828129

hm1

• Allelic Composition: Bhlha15^{tm3(cre/ERT2)Skz}/Bhlha15^{tm3(cre/ERT2)Skz}
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6

• ♀: phenotype observed in females
• ♂: phenotype observed in males
• N: normal phenotype

cellular

abnormal autophagy ( J:239144 )

• acinar cells have high levels of autophagic vacuoles

digestive/alimentary system

abnormal pancreatic acinar cell morphology ( J:239144 )

• acinar cells lack an apical-basal polarity

• nuclei and rough endoplasmic reticulum fail to accumulate at the basal pole and zymogen granules fail to cluster at the apical pole

• acini lumens are highly dilated with reduced secretion of zymogens into ductal system

• acini cells are small and lack a cortical and terminal actin web

• acinar cells lack connexin32-containing gap junctions

• acinar cells have high levels of autophagic vacuole

abnormal pancreatic acinar cell zymogen granule morphology ( J:239144 )

• diameters of zymogen granules are decreased in size

abnormal pancreatic acinar cell physiology ( J:239144 )

• acini lumens are highly dilated with reduced secretion of zymogens into ductal system

decreased pancreatic amylase secretion ( J:239144 )

• acinar cells are unresponsive to cholecytokinin induction of exocytosis as measured by amylase secretion

endocrine/exocrine glands

abnormal pancreatic acinar cell morphology ( J:239144 )

• acinar cells lack an apical-basal polarity

• nuclei and rough endoplasmic reticulum fail to accumulate at the basal pole and zymogen granules fail to cluster at the apical pole

• acini lumens are highly dilated with reduced secretion of zymogens into ductal system

• acini cells are small and lack a cortical and terminal actin web

• acinar cells lack connexin32-containing gap junctions

• acinar cells have high levels of autophagic vacuole

abnormal pancreatic acinar cell zymogen granule morphology ( J:239144 )

• diameters of zymogen granules are decreased in size

abnormal pancreatic acinar cell physiology ( J:239144 )

• acini lumens are highly dilated with reduced secretion of zymogens into ductal system

decreased pancreatic amylase secretion ( J:239144 )

• acinar cells are unresponsive to cholecytokinin induction of exocytosis as measured by amylase secretion

homeostasis/metabolism

abnormal autophagy ( J:239144 )

• acinar cells have high levels of autophagic vacuoles

Genotype
MGI:3821739

cn2

• Allelic Composition: Kras^tm4Tyj/Kras^tm4Tyj; Bhlha15^{tm3(cre/ERT2)Skz}/Bhlha15⁺
• Genetic Background: involves: 129S1/Sv * 129S4/SvJae * 129X1/SvJ

neoplasm

increased pancreatic intraepithelial neoplasia incidence ( J:142189 )

• 2 months after injection with tamoxifen, mice exhibit focal low grade pancreatic intraepithelial neoplasia (PanIN) originating from acinar cells that progresses to carcinoma in situ in some cases by 4 to 12 months following injection with tamoxifen

• tamoxifen treated mice exhibit lesions that progress from normal acinar parenchyma to acinar-ductal metaplastic structures to PanIN with biphenotypic exocrine differentiation

• tamoxifen treated mice exhibit highly proliferative acinar derived PanIN

endocrine/exocrine glands

increased pancreatic intraepithelial neoplasia incidence ( J:142189 )

• 2 months after injection with tamoxifen, mice exhibit focal low grade pancreatic intraepithelial neoplasia (PanIN) originating from acinar cells that progresses to carcinoma in situ in some cases by 4 to 12 months following injection with tamoxifen

• tamoxifen treated mice exhibit lesions that progress from normal acinar parenchyma to acinar-ductal metaplastic structures to PanIN with biphenotypic exocrine differentiation

• tamoxifen treated mice exhibit highly proliferative acinar derived PanIN

Genotype
MGI:5827856

cn3

• Allelic Composition: Bhlha15^{tm3(cre/ERT2)Skz}/Bhlha15^{tm3(cre/ERT2)Skz}; Tg(CAG-Bhlha15)1Skz/0
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6

endocrine/exocrine glands

endocrine/exocrine gland phenotype ( J:239144 )

N • transgene expression, following exposure to tamoxifen, rescues pancreatic acinar cells from dilation of acini lumens, loss of actin cytoskeleton, loss of connexin32-containing gap junctions, impaired exocytosis, autophagic vacuoles and decreases in acini cell size seen in homozygous Bhlha15^{tm3(cre/ERT2)Skz} mice

N • transgene expression, following exposure to tamoxifen, allows acinar cells to re-establish apical-basal polarity disrupted in homozygous Bhlha15^{tm3(cre/ERT2)Skz} mice; zymogen granules localize to apical pole and increase in size to wild-type diameters

Genotype
MGI:6154165

cn4

• Allelic Composition: Bhlha15^{tm3(cre/ERT2)Skz}/?; Gt(ROSA)26Sor^{tm4(ACTB-tdTomato,-EGFP)Luo}/?; Trip11^tm1.1Psmi/Trip11^tm1.2Psmi
• Genetic Background: involves: 129/Sv * C57BL/6

normal phenotype

no abnormal phenotype detected ( J:253969 )

• despite the absence of a gene invovled in vesicle transport, no swelling of the endoplasmic reticulum cisternae is found in the acinar cells of the adult pancreas