Mouse Genome Informatics
hm1
    Pdx1tm1Cvw/Pdx1tm1Cvw
involves: 129S1/Sv * 129X1/SvJ * Black Swiss
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• homozygotes can survive until at least 6.5 days post-partum (P6.5), but are not maintained longer for ethical reasons

digestive/alimentary system
• homozygotes show impaired posterior foregut development
• homozygotes show a blockage in differentiation of acinar cells
• 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
• at P1, mutant small intestines contain no milky gut contents and appear empty
• 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
• at P6.5, many homozygotes display a stomach/duodenal obstruction, as shown by stomach distension and failure of gastric emptying
• at 18.5 dpc and P1, the mutant pyloric sphincter appears twisted despite normal smooth muscle bands

endocrine/exocrine glands
• homozygotes show a blockage in differentiation of acinar cells
• 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
• at 11.5 dpc, the common bile duct is severely reduced in size
• homozygotes show a blockage in differentiation of islets
• homozygotes show a blockage in differentiation of mature beta-cells
• 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
• although P6.5 homozygotes contain milk in their stomachs, they weigh ~60% less than wild-type littermates
• homozygotes appear normal immediately after birth but show signs of growth retardation as early as P1

homeostasis/metabolism
• homozygotes show signs of dehydration as early as P1
• by P6.5, homozygotes are severely dehydrated

liver/biliary system
• at 11.5 dpc, the common bile duct is severely reduced in size
• at 11.5 dpc, the mutant liver primordium is juxtaposed to the duodenum

integument
• at P6.5, homozygotes have very little fur relative to wild-type mice
• at P6.5, homozygotes have a thin and cracking skin

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

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


Mouse Genome Informatics
ht2
    Pdx1tm1Cvw/Pdx1+
involves: 129S1/Sv * 129X1/SvJ * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
endocrine/exocrine glands
N
• beta cell size is normal (J:165268)
• mice exhibit beta cell apoptosis unlike in wild-type mice
• mice exhibit an increase in the number of small islets with a decrease in medium and large sized islets compared with wild-type mice
• beta cells exhibit increased endoplasmic reticulum stress that results in apoptosis unlike in wild-type mice
• beta cell replication and apoptosis are increased compared to in wild-type mice
• in response to glucose in mice and isolated cells

homeostasis/metabolism
• in response to glucose in mice and isolated cells

cellular
• mice exhibit beta cell apoptosis unlike in wild-type mice


Mouse Genome Informatics
ht3
    Pdx1tm1Cvw/Pdx1tm1.1Stof
involves: 129/Sv * 129S1/Sv * 129X1/SvJ * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
endocrine/exocrine glands
• small compared to in wild-type mice but not as small as in Pdx1tm1Cvw homozygotes
• decreased weight compared to in wild-type mice but not as much as in Pdx1tm1Cvw homozygotes

homeostasis/metabolism
• at birth


Mouse Genome Informatics
cn4
    Nkx6-1tm1.1Msan/Nkx6-1+
Pdx1tm1Cvw/Pdx1+
Tg(Neurog3-cre)C1Able/0

involves: 129/Sv * C57BL/6 * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
endocrine/exocrine glands
• mice exhibit an increase in the glucagon to insulin cell ratio as in Pdx1tm1Cvw heterozygotes
• as in Pdx1tm1Cvw heterozygotes
• as in Pdx1tm1Cvw heterozygotes


Mouse Genome Informatics
cn5
    Pdx1tm1Cvw/Pdx1tm4Cvw
Tg(Ins2-cre)25Mgn/0

involves: 129S1/Sv * 129X1/SvJ * Black Swiss * C57BL/6 * DBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
endocrine/exocrine glands
• proliferation of Pdx1- cells is decreased compared to in wild-type pancreas
• beginning at E18.5, the number of glucagon+ cells is increased
• by one month of age mice are overtly diabetic with increased numbers of glucagon+ cells
• proliferation of glucagon+ cells is increased
• the number of insulin+ cells decreases as the number of glucagon+ cells increases
• the proliferation of insulin+ cells is decreased
• by one month of age mice are overtly diabetic with decreased insulin immunoreactivity in remaining insulin+ cells
• by one month of age mice are overtly diabetic with increased numbers of somatostatin+ cells
• glucagon+ and somatostatin+ cells are scattered throughout the islet instead of localized to the periphery as in wild-type mice

homeostasis/metabolism
• insulin levels following administration of glucose are lower in males and females compared to wild-type mice
• unlike male mice, females exhibit only mild glucose intolerance compared to wild-type females

Mouse Models of Human Disease
OMIM IDRef(s)
Diabetes Mellitus, Insulin-Dependent; IDDM 222100 J:130389


Mouse Genome Informatics
cx6
    Pdx1tm1Cvw/Pdx1+
SpopGt(BGB118)Byg/Spop+

involves: 129P2/OlaHsd * 129S1/Sv * 129X1/SvJ * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
endocrine/exocrine glands
N
• beta cell mass and the distribution of islet size are normalized unlike in either single heterozygote (J:165268)
• mice do not exhibit beta cell apoptosis unlike either single heterozygote (J:165268)
• beta cell size is decreased compared to in wild-type mice or either single heterozygote
• endoplasmic reticulum stress is reduced compared to in Pdx1tm1Cvw heterozygote
• beta cell replication is increased compared to in wild-type mice
• glucose-stimulated insulin secretion is reduced compared to in wild-type mice but not as severely as in Pdx1tm1Cvw heterozygote

homeostasis/metabolism
• glucose-stimulated insulin secretion is reduced compared to in wild-type mice but not as severely as in Pdx1tm1Cvw heterozygote
• compared with Pdx1tm1Cvw heterozygote


Mouse Genome Informatics
cx7
    Pdx1tm1Cvw/Pdx1+
Pbx1tm1Mlc/Pbx1+

involves: 129S6/SvEvTac * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
endocrine/exocrine glands
• disrupted architecture, inappropriate cell types interspersed with beta cells

growth/size/body
• 9-10 weeks

homeostasis/metabolism
• onset between 9-10 weeks, progresses to overt diabetes

renal/urinary system

Mouse Models of Human Disease
OMIM IDRef(s)
Diabetes Mellitus, Noninsulin-Dependent; NIDDM 125853 J:75811