Phenotypes associated with this allele

• Allele Symbol: Pdx1^tm1Macd
• Allele Name: targeted mutation 1, Raymond J MacDonald
• Allele ID: MGI:2388676
• Summary: 8 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Pdx1^tm1Macd/Pdx1^tm1Macd	involves: 129S1/Sv * 129X1/SvJ	MGI:4356149
ht2	Pdx1^tm1Macd/Pdx1^+	involves: 129S1/Sv * 129X1/SvJ	MGI:3655707
cn3	Neurog3^tm1.1(cre/ERT)Ggu/Neurog3^+ Pdx1^tm1Macd/Pdx1^+ Tg(tetO-Myt1)2Ggu/0	involves: 129S1/Sv * 129S6/SvEvTac * 129X1/SvJ	MGI:3809541
cx4	Pdx1^tm1Macd/Pdx1^+ Tg(tetO-Neurog3)8Ggu/0	involves: 129S1/Sv * 129X1/SvJ	MGI:3809542
cx5	Pdx1^tm1Macd/Pdx1^+ Tg(tetO-Myt1)2Ggu/0	involves: 129S1/Sv * 129X1/SvJ	MGI:3809543
cx6	Pdx1^tm1Macd/Pdx1^+ Tg(tetO-Sox17,-EGFP)1Jaw/0	involves: 129S1/Sv * 129X1/SvJ	MGI:4356153
cx7	Pdx1^tm1Macd/Pdx1^tm1Macd Tg(tetO-Ipf1,EGFP)956.6Macd/0	involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * SJL	MGI:3655708
cx8	Pdx1^tm1Macd/Pdx1^tm1Macd Tg(tetO-Ipf1,lacZ)958.1Macd/0	involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * SJL	MGI:3655709

Genotype
MGI:4356149

hm1

• Allelic Composition: Pdx1^tm1Macd/Pdx1^tm1Macd
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ

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

liver/biliary system

liver/biliary system phenotype ( J:151981 )

N • mice exhibit normal development of the gall bladder, collecting ducts, and common duct

Genotype
MGI:3655707

ht2

• Allelic Composition: Pdx1^tm1Macd/Pdx1⁺
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ

homeostasis/metabolism

impaired glucose tolerance ( J:79206 , J:101742 )

• heterozygotes display partially impaired glucose tolerance compared to wild-type mice; doxycycline treatment has no effect (J:79206)

• heterozygotes display partially impaired early response to glucose challenge compared to wild-type mice; ability to recover after glucose challenge is impaired (J:101742)

Genotype
MGI:3809541

cn3

• Allelic Composition: Neurog3^{tm1.1(cre/ERT)Ggu}/Neurog3⁺; Pdx1^tm1Macd/Pdx1⁺; Tg(tetO-Myt1)2Ggu/0
• Genetic Background: involves: 129S1/Sv * 129S6/SvEvTac * 129X1/SvJ

endocrine/exocrine glands

abnormal pancreatic islet morphology ( J:136131 )

• fewer cells are induced to produce glucagons than in Pdx1^tm1Macd/Pdx1⁺ Tg(tetO-Neurog3)8Ggu mice

Genotype
MGI:3809542

cx4

• Allelic Composition: Pdx1^tm1Macd/Pdx1⁺; Tg(tetO-Neurog3)8Ggu/0
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ

endocrine/exocrine glands

abnormal pancreas development ( J:136131 )

• epithelial to mesenchyme transition is induced in the pancreas

• mice exhibit precocious endocrine differentiation, converting nearly all pancreatic cells to glucagon producing cells after E11.5

Genotype
MGI:3809543

cx5

• Allelic Composition: Pdx1^tm1Macd/Pdx1⁺; Tg(tetO-Myt1)2Ggu/0
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ

endocrine/exocrine glands

abnormal pancreas development ( J:136131 )

• mice exhibit precocious endocrine differentiation, converting 1.8-fold more pancreatic cells to glucagon producing, immature alpha cells at E11.5 than in Pdx1^tm1Macd heterozygotes

• however, this conversion is not sustained later in development as E18.5, only rare glucagons producing cells are found

Genotype
MGI:4356153

cx6

• Allelic Composition: Pdx1^tm1Macd/Pdx1⁺; Tg(tetO-Sox17,-EGFP)1Jaw/0
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ

digestive/alimentary system

digestive/alimentary phenotype ( J:151981 )

N • when treated with doxycycline until E12.5, mice exhibit normal no ectopic mass at the pyloric-duodenum junction

abnormal digestive system morphology ( J:151981 )

• at E16.5, mice exhibit a large mass at the pyloric junction between the stomach and duodenum unlike in control mice

• at E16.5, mice exhibit many ectopic duct-like structures unlike in control mice

pancreatic acinar hypoplasia ( J:151981 )

• at 6 weeks, in mice treated with doxycycline until E12.5

exocrine pancreas hyperplasia ( J:151981 )

• at 6 weeks, mice treated with doxycycline until E12.5 exhibit a massive expansion of ductal tissues compared to in control mice

abnormal stomach morphology ( J:151981 )

• at E16.5, mice exhibit hyperplastic stomach epithelium and mesenchyme

stomach epithelial hyperplasia ( J:151981 )

• hyperplastic at E16.5

endocrine/exocrine glands

abnormal pancreas morphology ( J:151981 )

• when treated with doxycycline until E12.5, endocrine cells are replaced with ductal cells unlike in control mice

pancreatic acinar hypoplasia ( J:151981 )

• at 6 weeks, in mice treated with doxycycline until E12.5

exocrine pancreas hyperplasia ( J:151981 )

• at 6 weeks, mice treated with doxycycline until E12.5 exhibit a massive expansion of ductal tissues compared to in control mice

abnormal endocrine pancreas morphology ( J:151981 )

• at 6 weeks, mature endocrine cells are nearly absent in mice treated with doxycycline until E12.5 unlike in control mice

abnormal pancreas development ( J:151981 )

• at E10.5, the remnant of the dorsal and ventral pancreatic bud is fused to the gut tube unlike in control mice

small pancreas ( J:151981 )

• at E16.5, only a pancreatic remnant remains

liver/biliary system

liver/biliary system phenotype ( J:151981 )

N • liver bud development and biliary epithelium are normal

growth/size/body

exocrine pancreas hyperplasia ( J:151981 )

• at 6 weeks, mice treated with doxycycline until E12.5 exhibit a massive expansion of ductal tissues compared to in control mice

Genotype
MGI:3655708

cx7

• Allelic Composition: Pdx1^tm1Macd/Pdx1^tm1Macd; Tg(tetO-Ipf1,EGFP)956.6Macd/0
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * SJL

homeostasis/metabolism

increased glucagon secretion ( J:101742 )

• in doxycycline-treated mice there is an increase in glucagons-positive cells

decreased insulin secretion ( J:101742 )

• there is a marked reduction in insulin in pancreata of doxycycline-treated mice; after withdrawal of doxycycline, insulin +ve cells are detected in islets of smaller islet-like cell clusters

decreased circulating glucose level ( J:101742 )

• 14 days after doxycycline withdrawal after 14 days of treatment resulted in a significant decrease in blood glucose levels with 4/5 mice becoming normoglycemic by 28 days

increased circulating glucose level ( J:79206 )

• with doxycycline treatment for 21 day, adult rescue mice show a 4-fold increase in fasting blood glucose to diabetic levels

impaired glucose tolerance ( J:79206 , J:101742 )

• adult transgenic rescue animals treated with doxycycline for 14 days exhibit a defective response to glucose challenge compared to wild-type, non mutant transgenic, or untreated rescue mice (J:79206)

• when adult mice are treated with doxycycline for 0, 7, 14, or 21 days, mice show an increased early glucose response within 7 days of start of treatment and ability to recover from glucose challenge is impaired compared to untreated transgenics where glucose levels recover to basal levels within 3 hours; by 14 days of doxycycline treatment, mice have diabetes (J:101742)

endocrine/exocrine glands

abnormal pancreatic beta cell morphology ( J:101742 )

• after 14 or 28 days of dox treatment there are, still present, beta cells which lack insulin

small pancreatic islets ( J:101742 )

• after dox treatment for 14 days, there is a significant decrease in islet area compared to wild-type

abnormal pancreas development ( J:79206 )

• pancreas of transgenic rescue newborn mice is 50% the size of a normal wild-type neonatal pancreas

• treatment of pregnant mice with doxycycline from the first day of pregnancy through parturition prevents formation of the pancreas in mice with the transgenic rescue genotype

• treatment on E11.5 arrests pancreatic development ~36 hours later; at birth the underdeveloped remnant consisted of a large and extended duct with several terminal, aborted, ductal buds with ducts lined with a single layer of primitive epithelial cells and with no acinar or islet tissue

increased glucagon secretion ( J:101742 )

• in doxycycline-treated mice there is an increase in glucagons-positive cells

decreased insulin secretion ( J:101742 )

• there is a marked reduction in insulin in pancreata of doxycycline-treated mice; after withdrawal of doxycycline, insulin +ve cells are detected in islets of smaller islet-like cell clusters

cellular

increased cell proliferation ( J:101742 )

• foci of duct proliferation are present in mice after 14 days of doxycycline treatment and become more prominent with continued treatment

Genotype
MGI:3655709

cx8

• Allelic Composition: Pdx1^tm1Macd/Pdx1^tm1Macd; Tg(tetO-Ipf1,lacZ)958.1Macd/0
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * SJL

homeostasis/metabolism

impaired glucose tolerance ( J:103522 )

• transgenic mice gradually attain an impaired glucose tolerance response to glucose challenge

endocrine/exocrine glands

abnormal pancreas development ( J:103522 )

• when dams are treated with doxycycline from conception through birth, only small epithelial remnants of the pancreas form; treatment at E7.5 or E8.5 results in the same phenotype

• doxycycline from E9.5 diminishes epithelial morphogenesis; treatement from E9.5 allows outgrowth of a linear epithelial tube with nascent invaginations representing initial primary branching

• treatment from E11.5 allows the formation of a larger crude duct-like structure with a few distal primary branches; treatement from E12.5 permits formation of extensive fine structure consisting of immature acini and associated small ductules

• with treatment from E12.5, pancreatic dorsal and ventral remnants composed of convoluted partially branched duct-like epithelium of columnar epithelium are present, and show a block at the stage of acinar cell formation

• examination of embryo ductal remnants from mice treated with dox from E11.5 show an absence of preacini; treatment from E12.5 results in a larger remnant with a smaller proportion of primitive duct; the epithelium is replaced by numerous eosinophilic clusters lacking ductal markers which are polarized, arranged around a central lumen and resemble immature acini

absent pancreas ( J:103522 )

• ~1/5 pups are born without a pancreas; rescue of pancreas formation is observed in ~80% of transgenic mice