Phenotypes associated with this allele

• Allele Symbol: Onecut1^tm1.1Mga
• Allele Name: targeted mutation 1.1, Maureen A Gannon
• Allele ID: MGI:3526029
• Summary: 3 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cn1	Onecut1^tm1.1Mga/Onecut1^tm1.1Mga Tg(Pdx1-cre)89.1Dam/0	involves: 129S6/SvEvTac * C57BL/6 * CBA * SJL	MGI:4413463
cn2	Onecut1^tm1.1Mga/Onecut1^tm1.1Mga Tg(Six3-cre)69Frty/0	involves: 129S6/SvEvTac * C57BL/6 * DBA/2	MGI:6384690
cn3	Onecut1^tm1.1Mga/Onecut1^tm1.1Mga Tg(Neurog3-cre)C1Able/0	involves: 129S6/SvEvTac * C57BL/6 * SJL	MGI:4413462

Genotype
MGI:4413463

cn1

• Allelic Composition: Onecut1^tm1.1Mga/Onecut1^tm1.1Mga; Tg(Pdx1-cre)89.1Dam/0
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6 * CBA * SJL

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

cellular

abnormal pancreatic primary cilium morphology ( J:155058 )

• at E18.5, primary cilia are decreased in number and do not protrude into the duct lumen unlike in wild-type mice

decreased pancreatic primary cilium number ( J:155058 )

• at E18.5, primary cilia are decreased in number and do not protrude into the duct lumen unlike in wild-type mice

• at E18.5 and 6 weeks of age, pancreatic ducts exhibit a dramatic decrease in cilia number compared with wild-type mice

endocrine/exocrine glands

abnormal pancreas morphology ( J:155058 )

• mice lacking cysts exhibit minimal branching in the dorsal pancreas and/or twisted irregular ducts and calcifications unlike in wild-type mice

abnormal pancreatic primary cilium morphology ( J:155058 )

• at E18.5, primary cilia are decreased in number and do not protrude into the duct lumen unlike in wild-type mice

decreased pancreatic primary cilium number ( J:155058 )

• at E18.5, primary cilia are decreased in number and do not protrude into the duct lumen unlike in wild-type mice

• at E18.5 and 6 weeks of age, pancreatic ducts exhibit a dramatic decrease in cilia number compared with wild-type mice

abnormal pancreatic acinus morphology ( J:155058 )

• from 3 to 6 weeks of age, mice exhibit pancreatitis with atrophy, loss of acinar tissue, and acinar inflammation unlike in wild-type mice

decreased pancreatic acinar cell number ( J:155058 )

• in mice with cysts

abnormal pancreatic duct morphology ( J:155058 )

• at E18.5, primary cilia are decreased in number and do not protrude into the duct lumen unlike in wild-type mice

• at E18.5 and 6 weeks of age, mice exhibit a dramatic decrease in cilia number compared with wild-type mice

• pancreatic ducts become highly tortuous unlike in wild-type mice

• pancreatic ducts exhibit periductal inflammation, hemorrhage, and fibrosis

dilated pancreatic duct ( J:155058 )

• by 6 weeks of age, the ductal epithelium is multilayered and dilated unlike in wild-type mice

exocrine pancreas atrophy ( J:155058 )

• from 3 to 6 weeks of age

decreased pancreatic alpha cell number ( J:155058 )

• at E18.5 but not E13.5 or E14.5

decreased pancreatic beta cell number ( J:155058 )

• at E18.5 but not E13.5 or E14.5

absent pancreatic islets ( J:155058 )

• mice lack definitive islets unlike wild-type mice

abnormal branching involved in pancreas development ( J:155058 )

• at E14.5, pancreatic epithelium has less branching than in wild-type mice and fails to fully extend towards the distal surrounding mesenchyme

• postnatally, pancreatic epithelium never fills the mesenchyme unlike in wild-type mice

calcified pancreas ( J:155058 )

• mice exhibit dystrophic calcifications in adjacent fat unlike in wild-type mice

pancreas cyst ( J:155058 )

• at E18.5, mice develop a single, fluid-filled cyst lined with cuboidal epithelium in the dorsal pancreas unlike wild-type mice

• by 6 weeks of age, 63% of mice exhibit large pancreatic cysts mainly in the dorsal pancreas unlike wild-type mice

pancreas fibrosis ( J:155058 )

• in pancreatic ducts

pancreatic acinar-to-ductal metaplasia ( J:155058 )

• by P2, all mice exhibit acinar to ductal metaplasia unlike wild-type mice

abnormal pancreas physiology ( J:155058 )

• at E17.5 and 6 weeks of age, proliferation of ductal cells is increased compared to in wild-type mice

pancreas inflammation ( J:155058 )

• from 3 to 6 weeks of age, mice exhibit pancreatitis with atrophy, loss of acinar tissue, and acinar inflammation unlike in wild-type mice

• mice exhibit neutrophils in peripancreatic fat; neutrophils in the lumen and ductal epithelium of smaller ducts; intraparenchymal mixed inflammatory infiltrate with neutrophils and lymphocytes, with areas of acinar injury; neutrophils scattered in periductal stroma; large ducts with erosion and acute inflammation unlike wild-type mice

homeostasis/metabolism

abnormal glucose homeostasis ( J:155058 )

• impaired glucose homeostasis worsens with age

increased circulating glucose level ( J:155058 )

• at P2 and 3.5 weeks of age, mice exhibit elevated random blood glucose levels compared with wild-type mice

• at 6 weeks of age, fasting blood glucose levels are higher than in wild-type mice

cardiovascular system

hemorrhage ( J:155058 )

• in pancreatic ducts

immune system

pancreas inflammation ( J:155058 )

• from 3 to 6 weeks of age, mice exhibit pancreatitis with atrophy, loss of acinar tissue, and acinar inflammation unlike in wild-type mice

• mice exhibit neutrophils in peripancreatic fat; neutrophils in the lumen and ductal epithelium of smaller ducts; intraparenchymal mixed inflammatory infiltrate with neutrophils and lymphocytes, with areas of acinar injury; neutrophils scattered in periductal stroma; large ducts with erosion and acute inflammation unlike wild-type mice

digestive/alimentary system

abnormal pancreatic acinus morphology ( J:155058 )

• from 3 to 6 weeks of age, mice exhibit pancreatitis with atrophy, loss of acinar tissue, and acinar inflammation unlike in wild-type mice

decreased pancreatic acinar cell number ( J:155058 )

• in mice with cysts

abnormal pancreatic duct morphology ( J:155058 )

• at E18.5, primary cilia are decreased in number and do not protrude into the duct lumen unlike in wild-type mice

• at E18.5 and 6 weeks of age, mice exhibit a dramatic decrease in cilia number compared with wild-type mice

• pancreatic ducts become highly tortuous unlike in wild-type mice

• pancreatic ducts exhibit periductal inflammation, hemorrhage, and fibrosis

dilated pancreatic duct ( J:155058 )

• by 6 weeks of age, the ductal epithelium is multilayered and dilated unlike in wild-type mice

exocrine pancreas atrophy ( J:155058 )

• from 3 to 6 weeks of age

growth/size/body

pancreas cyst ( J:155058 )

• at E18.5, mice develop a single, fluid-filled cyst lined with cuboidal epithelium in the dorsal pancreas unlike wild-type mice

• by 6 weeks of age, 63% of mice exhibit large pancreatic cysts mainly in the dorsal pancreas unlike wild-type mice

Genotype
MGI:6384690

cn2

• Allelic Composition: Onecut1^tm1.1Mga/Onecut1^tm1.1Mga; Tg(Six3-cre)69Frty/0
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6 * DBA/2

vision/eye

vision/eye phenotype ( J:200752 )

N • normal location, morphology and number of rods, cones, bipolar, Mueller, amacrine, and retinal ganglion cells at age P16 and 3 months

N • normal retinal outer (ONL) and inner (INL) nuclear layer and retinal inner plexiform (IPL) and ganglion cell (GCL) layer morphology at age P16

N • normal levels of apoptosis in retina at ages E14.5, E17.5 and P0

thin retina outer nuclear layer ( J:200752 )

• slightly thinner at age 5 months

• around 3x thinner at age 8 months

disorganized retina outer nuclear layer ( J:200752 )

• less tightly packed at age 5 months

retina outer nuclear layer degeneration ( J:200752 )

• slightly thinner at age 5 months

• around 3x thinner at age 8 months

abnormal retina outer plexiform layer morphology ( J:200752 )

• larger spaces between horizontal cells (HCs) with longer and thicker processes at age P16 and 3 months

• 85% reduction in Lim1+ HC precursors at age E14.5 and HCs at age E17.5

• normal non-random mosaic distribution pattern at age P16

thin retina outer plexiform layer ( J:200752 )

• thinner and sometimes absent at age P16 and 3 months

• 74% reduction in number of horizontal cells (HCs) at age P16

• virtually absent at age 5 months

decreased a-wave amplitude ( J:200752 )

• much smaller across all light intensities using dark-adapted flash ERG at age 5 months

decreased b-wave amplitude ( J:200752 )

• much smaller across all light intensities using dark-adapted flash ERG at age 5 months

• around 3x smaller across all light intensities using light-adapted flash ERG at age 5 months

• normal time to peak

Genotype
MGI:4413462

cn3

• Allelic Composition: Onecut1^tm1.1Mga/Onecut1^tm1.1Mga; Tg(Neurog3-cre)C1Able/0
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6 * SJL

endocrine/exocrine glands

endocrine/exocrine gland phenotype ( J:155058 )

N • mice exhibit normal beta cell differentiation

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:155058 )

N • mice exhibit normal glucose homeostasis