All Phenotypes Pdx1<tm2Cvw> MGI Mouse

Phenotypes associated with this allele

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Pdx1^tm2Cvw/Pdx1^tm2Cvw	involves: 129S1/Sv * 129X1/SvJ * Black Swiss	MGI:3584044
hm2	Pdx1^tm2Cvw/Pdx1^tm2Cvw	involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * DBA	MGI:3703918
ht3	Pdx1^tm2Cvw/Pdx1⁺	involves: 129S1/Sv * 129X1/SvJ * Black Swiss	MGI:3584045
ht4	Pdx1^tm2Cvw/Pdx1⁺	involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * DBA	MGI:3703987
ht5	Pdx1^tm2Cvw/Pdx1⁺	involves: 129/Sv * Black Swiss	MGI:3811336
ht6	Pdx1^tm2Cvw/Pdx1^tm3Cvw	involves: 129/Sv * C57BL/6 * DBA * FVB/N	MGI:3703988
cx7	Pdx1^tm2Cvw/Pdx1⁺ Slc2a4^tm1Mch/Slc2a4⁺	involves: 129/Sv * Black Swiss * C57BL/6 * SJL	MGI:3811338

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

mortality/aging

postnatal lethality, complete penetrance ( J:32017 )

• homozygotes can survive until at least 6.5 days post-partum (P6.5), but are not maintained longer for ethical reasons

digestive/alimentary system

abnormal foregut morphology ( J:32017 )

• homozygotes show impaired posterior foregut development

abnormal pancreatic acinar cell morphology ( J:32017 )

• homozygotes show a blockage in differentiation of acinar cells

abnormal pancreatic duct morphology ( J:32017 )

• homozygotes exhibit normal initial generation and outgrowth of dorsal and ventral pancreatic ducts

• however, at 11.5 dpc, homozygotes lack the discrete outgrowth derived from the ventral pancreatic duct

• also at 11.5 dpc, the dorsal pancreatic outgrowth is replaced by an extra short ductular structure which persists into perinatal stages and undergoes limited proliferation and outgrowth as well as abnormal branching

• this ductular tree lacks insulin and amylase-positive cells and contains glucagons-expressing cells instead

abnormal small intestine morphology ( J:32017 )

• at P1, mutant small intestines contain no milky gut contents and appear empty

abnormal duodenum morphology ( J:32017 )

• at 18.5 dpc and P1, homozygotes exhibit a malformed stomach/duodenum junction relative to wild-type mice

• in most mutants, the rostral-most duodenum forms an undulated cavity lacking villi, and mature Brunner's glands, with a smooth cuboidal (rather than columnar) epithelium lining that is continuous with the common bile duct and dorsal pancreatic ductule

• a few mutants lack this undulated cavity but still contain abnormal smooth cuboidal epithelium

• 5 of 6 homozygotes show altered gut lumen architecture with a spiraled (rather than fairly straight) tube and several tight lumen constrictions

• just distal to the malformed rostral duodenum, homozygotes contain apparently normal villi, enterocytes and most enteroendocrine cell types; however, the numbers of enteroendocrine cells are markedly reduced in mutant villi

• homozygotes exhibit a "duodenal" gut tube of wild-type length; no extensive cell death is detected at any stage of development

abnormal stomach morphology ( J:32017 )

• at P6.5, many homozygotes display a stomach/duodenal obstruction, as shown by stomach distension and failure of gastric emptying

abnormal pyloric sphincter morphology ( J:32017 )

• at 18.5 dpc and P1, the mutant pyloric sphincter appears twisted despite normal smooth muscle bands

endocrine/exocrine glands

abnormal pancreatic acinar cell morphology ( J:32017 )

• homozygotes show a blockage in differentiation of acinar cells

abnormal pancreatic duct morphology ( J:32017 )

• homozygotes exhibit normal initial generation and outgrowth of dorsal and ventral pancreatic ducts

• however, at 11.5 dpc, homozygotes lack the discrete outgrowth derived from the ventral pancreatic duct

• this ductular tree lacks insulin and amylase-positive cells and contains glucagons-expressing cells instead

abnormal bile duct development ( J:32017 )

• at 11.5 dpc, the common bile duct is severely reduced in size

abnormal pancreatic islet morphology ( J:32017 )

• homozygotes show a blockage in differentiation of islets

abnormal pancreatic beta cell differentiation ( J:32017 )

• homozygotes show a blockage in differentiation of mature beta-cells

absent pancreas ( J:32017 )

• at 18.5 dpc, homozygotes display complete lack of pancreatic tissues

• in contrast, the liver, gall bladder, spleen, stomach, common bile duct, and other viscera are present and normal

growth/size/body

decreased body weight ( J:32017 )

• although P6.5 homozygotes contain milk in their stomachs, they weigh ~60% less than wild-type littermates

postnatal growth retardation ( J:32017 )

• homozygotes appear normal immediately after birth but show signs of growth retardation as early as P1

homeostasis/metabolism

dehydration ( J:32017 )

• homozygotes show signs of dehydration as early as P1

• by P6.5, homozygotes are severely dehydrated

liver/biliary system

abnormal bile duct development ( J:32017 )

• at 11.5 dpc, the common bile duct is severely reduced in size

abnormal liver development ( J:32017 )

• at 11.5 dpc, the mutant liver primordium is juxtaposed to the duodenum

integument

sparse hair ( J:32017 )

• at P6.5, homozygotes have very little fur relative to wild-type mice

thin skin ( J:32017 )

• at P6.5, homozygotes have a thin and cracking skin

muscle

abnormal pyloric sphincter morphology ( J:32017 )

• at 18.5 dpc and P1, the mutant pyloric sphincter appears twisted despite normal smooth muscle bands

cellular

abnormal pancreatic beta cell differentiation ( J:32017 )

• homozygotes show a blockage in differentiation of mature beta-cells

Allelic Composition	Pdx1^tm2Cvw/Pdx1^tm2Cvw
Genetic Background	involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * DBA

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Pdx1^tm2Cvw mutation (1 available); any Pdx1 mutation (35 available)

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

digestive/alimentary system

abnormal stomach enteroendocrine cell morphology ( J:104617 )

• dramatic reduction in gastrin-producing cells is observed in antral stomach (100% loss at P7)

• GIP- (gastric inhibitory polypeptide) producing cells reduced in number by 96.5% by E18.5; GIP-producing cells are decreased 77.8% in number compared to Pdx^tm4.1Cvw homozygotes

abnormal intestine morphology ( J:104617 )

• rostral most duodenal cavity often has undulating appearance, lacking villi

abnormal stomach pyloric region morphology ( J:104617 )

• many homozygotes show pyloric atresia

distended stomach ( J:104617 )

• at P1, many homozygotes display stomach distention caused by poor gastric emptying

endocrine/exocrine glands

abnormal stomach enteroendocrine cell morphology ( J:104617 )

• dramatic reduction in gastrin-producing cells is observed in antral stomach (100% loss at P7)

• GIP- (gastric inhibitory polypeptide) producing cells reduced in number by 96.5% by E18.5; GIP-producing cells are decreased 77.8% in number compared to Pdx^tm4.1Cvw homozygotes

Allelic Composition	Pdx1^tm2Cvw/Pdx1⁺
Genetic Background	involves: 129S1/Sv * 129X1/SvJ * Black Swiss

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Pdx1^tm2Cvw mutation (1 available); any Pdx1 mutation (35 available)

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

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:75664 )

N	• heterozygotes display a normal fasting blood glucose and pancreatic insulin content relative to wild-type mice

increased glucagon secretion ( J:75664 )

• heterozygotes show a 29% increase in pancreatic glucagon content relative to wild-type mice

decreased insulin secretion ( J:75664 )

• perfused pancreata of heterozygotes secrete ~45% less insulin when stimulated with 16.7 mM glucose; the K_m for insulin release is similar to that of wild-type mice

• also, perfused pancreata show a significantly reduced insulin release in response to 20 mM KCl (66%) and to 10 mM 2-ketoisocaproate (KIC; 61%)

• insulin secretion in response to 20 mM arginine is unchanged; the response to 10 nM glucagon-like peptide-1 is only slightly increased

• reduced insulin secretory responses to glucose, KIC, and KCl, as well as reduced generation of NAD(P)H, suggest mitochondrial dysfunction and/or abnormal mobilization of Ca²⁺

impaired glucose tolerance ( J:75664 )

• both heterozygous males and females display impaired glucose clearance after i.p. glucose administration; males are more affected than females

• impaired glucose tolerance is noted as early as 8 weeks and becomes more pronounced with increasing age (16-25 weeks)

• notably, 30% of male and 20% of female heterozygotes exhibit normal glucose tolerance; however, their plasma insulin levels are reduced to levels similar to those found in heterozygotes with impaired glucose tolerance

endocrine/exocrine glands

increased glucagon secretion ( J:75664 )

• heterozygotes show a 29% increase in pancreatic glucagon content relative to wild-type mice

abnormal pancreatic beta cell physiology ( J:75664 )

• mutant islets show a marked (55%) but variable reduction in SLC2A2 expression relative to wild-type islets; in contrast, glucokinase expression remains unchanged

• however, at 16-18-weeks, heterozygotes show normal islet morphology and a normal ratio of beta to alpha or delta cells

decreased amylin secretion ( J:75664 )

• at 25-40 weeks, heterozygotes show a 32% reduction in pancreatic islet amyloid polypeptide (IAPP) content relative to wild-type mice

decreased insulin secretion ( J:75664 )

• perfused pancreata of heterozygotes secrete ~45% less insulin when stimulated with 16.7 mM glucose; the K_m for insulin release is similar to that of wild-type mice

• also, perfused pancreata show a significantly reduced insulin release in response to 20 mM KCl (66%) and to 10 mM 2-ketoisocaproate (KIC; 61%)

• insulin secretion in response to 20 mM arginine is unchanged; the response to 10 nM glucagon-like peptide-1 is only slightly increased

• reduced insulin secretory responses to glucose, KIC, and KCl, as well as reduced generation of NAD(P)H, suggest mitochondrial dysfunction and/or abnormal mobilization of Ca²⁺

cellular

abnormal mitochondrial physiology ( J:75664 )

• in addition, heterozygotes exhibit reduced insulin response to KIC, suggesting impaired mitochondrial metabolism and/or K⁺_ATP channel-dependent stimulus-secretion coupling

abnormal tricarboxylic acid cycle ( J:75664 )

• heterozygous islets display a 30% reduction in NAD(P)H generation in response to 20 mM glucose

Allelic Composition	Pdx1^tm2Cvw/Pdx1⁺
Genetic Background	involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * DBA

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Pdx1^tm2Cvw mutation (1 available); any Pdx1 mutation (35 available)

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

homeostasis/metabolism

impaired glucose tolerance ( J:104617 )

• at 8-11 weeks of age, mice show severely impaired glucose clearance compared to wild-type

Allelic Composition	Pdx1^tm2Cvw/Pdx1⁺
Genetic Background	involves: 129/Sv * Black Swiss

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Pdx1^tm2Cvw mutation (1 available); any Pdx1 mutation (35 available)

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

endocrine/exocrine glands

decreased insulin secretion ( J:97234 )

• insulin levels are lower than wild-type for at least 2 hours after administration of glucose

• insulin-to-glucose ratios are at about three times lower than controls 15 minutes into glucose tolerance tests

homeostasis/metabolism

decreased insulin secretion ( J:97234 )

• insulin levels are lower than wild-type for at least 2 hours after administration of glucose

• insulin-to-glucose ratios are at about three times lower than controls 15 minutes into glucose tolerance tests

impaired glucose tolerance ( J:97234 )

• mice have elevated blood glucose levels for at least 2 hours after glucose administration averaging around 350 mg/dl

Allelic Composition	Pdx1^tm2Cvw/Pdx1^tm3Cvw
Genetic Background	involves: 129/Sv * C57BL/6 * DBA * FVB/N

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Pdx1^tm2Cvw mutation (1 available); any Pdx1 mutation (35 available)
Pdx1^tm3Cvw mutation (0 available); any Pdx1 mutation (35 available)

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

mortality/aging

postnatal lethality, complete penetrance ( J:104617 )

• most mice die by P9, and all are dead by P17

growth/size/body

postnatal growth retardation ( J:104617 )

• by 2 days postnatal, mice show growth retardation

endocrine/exocrine glands

exocrine pancreatic insufficiency ( J:104617 )

• dorsal outgrowth found in place of pancreas lacks insulin, somatostatin, and PP, as well as exocrine markers like amylase

abnormal pancreas development ( J:104617 )

• pancreas is replaced by small rudiment protruding from duodenal wall; rudiment has glucagon-producing cells at tips of ductular tree that shows limited branching

• at E12, dorsal pancreatic bud is smaller with no evidence of branching morphogenesis compared to wild-type; no separate ventral pancreatic bud is present

digestive/alimentary system

abnormal enteroendocrine cell morphology ( J:104617 )

• GIP-producing cells are decreased 63.4% compared to Pdx^tm4.1Cvw homozygotes

exocrine pancreatic insufficiency ( J:104617 )

• dorsal outgrowth found in place of pancreas lacks insulin, somatostatin, and PP, as well as exocrine markers like amylase

homeostasis/metabolism

dehydration ( J:104617 )

• by 2 days postnatal, mice show dehydration

Allelic Composition	Pdx1^tm2Cvw/Pdx1⁺ Slc2a4^tm1Mch/Slc2a4⁺
Genetic Background	involves: 129/Sv * Black Swiss * C57BL/6 * SJL

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Pdx1^tm2Cvw mutation (1 available); any Pdx1 mutation (35 available)
Slc2a4^tm1Mch mutation (0 available); any Slc2a4 mutation (35 available)

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

endocrine/exocrine glands

pancreatic islet hyperplasia ( J:97234 )

• islet cell hyperplasia becomes prominent by 40 weeks of age and persists until late in life

• islet mass increases 6- to 8-fold by 21 months of age

• this increase is due only to an increase in beta-cell mass

decreased insulin secretion ( J:97234 )

• insulin levels are lower than wild-type for at least 2 hours after administration of glucose

• insulin-to-glucose ratios are at least three times lower than controls 15 minutes into glucose tolerance tests

• insulin secretion is also significantly decreased during in situ pancreas infusion with either 5.6 mM glucose or 20mM arginine

• there is less insulin per mg of pancreatic protein in mice 31 to 47 weeks in age

homeostasis/metabolism

decreased insulin secretion ( J:97234 )

• insulin levels are lower than wild-type for at least 2 hours after administration of glucose

• insulin-to-glucose ratios are at least three times lower than controls 15 minutes into glucose tolerance tests

• insulin secretion is also significantly decreased during in situ pancreas infusion with either 5.6 mM glucose or 20mM arginine

• there is less insulin per mg of pancreatic protein in mice 31 to 47 weeks in age

increased circulating glucose level ( J:97234 )

• fasting glucose levels rise with age so that by 48 weeks of age half of these mice have a blood glucose level higher than 150mg/dl

• mean glucose levels are significantly higher than controls by 32 weeks of age

decreased circulating insulin level ( J:97234 )

• insulin levels are reduced with age

impaired glucose tolerance ( J:97234 )

• mice have extremely elevated blood glucose levels for at least 2 hours after glucose administration averaging around 475 mg/dl

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