Phenotypes associated with this allele

• Allele Symbol: Ptger4^tm1Bhk
• Allele Name: targeted mutation 1, Beverly H Koller
• Allele ID: MGI:2137850
• Summary: 2 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Ptger4^tm1Bhk/Ptger4^tm1Bhk	involves: 129P2/OlaHsd * 129S/SvEv	MGI:2175007
hm2	Ptger4^tm1Bhk/Ptger4^tm1Bhk	involves: 129P2/OlaHsd * C57BL/6 * DBA/2	MGI:3590045

Genotype
MGI:2175007

hm1

• Allelic Composition: Ptger4^tm1Bhk/Ptger4^tm1Bhk
• Genetic Background: involves: 129P2/OlaHsd * 129S/SvEv

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

mortality/aging

postnatal lethality, complete penetrance ( J:44108 )

• homozygotes obtained from crosses with 129S/SvEv mice are alive at 12 hours after birth; however, most of them die within 48 hours after birth

• no homozygotes survive to weaning

• Background Sensitivity: selective breeding of the 5% of homozygotes that survive on a mixed genetic (129P2/OlaHsd x C57BL/6 x DBA/2) background results in a 21% survival rate

growth/size/body

increased lung weight ( J:44108 )

• homozygotes exhibit a higher lung-to-body-weight ratio relative to wild-type mice

cardiovascular system

abnormal capillary morphology ( J:44108 )

• mutant lungs display congestion of pulmonary septal capillaries

liver vascular congestion ( J:44108 )

• such changes are suggestive of acute ischemia secondary to heart failure

• in a number of homozygotes that die at >24 h after birth, mutant livers display changes compatible with passive congestion

pulmonary vascular congestion ( J:44108 )

• mutant lungs exhibit congestion of pulmonary septal capillaries

patent ductus arteriosus ( J:44108 )

• although the DA appears constricted relative to the fetal DA at 3 hrs after birth, homozygous newborns exhibit obvious patency of the DA at both 7 and 12 hrs after birth

• at 12 hrs, swelling of the intima absent and the endothelium remains a single layer of cells contiguous with that of the aorta

lung hemorrhage ( J:44108 )

• homozygotes exhibit hemorrhaging into the alveolar spaces and major respiratory ducts

pulmonary alveolar hemorrhage ( J:44108 )

decreased pulmonary vascular resistance ( J:44108 )

• homozygotes show a postnatal drop in pulmonary vascular resistance

left-to-right shunt ( J:44108 )

• mutant lungs display a left-to-right shunt of blood

respiratory system

lung hemorrhage ( J:44108 )

• homozygotes exhibit hemorrhaging into the alveolar spaces and major respiratory ducts

pulmonary alveolar hemorrhage ( J:44108 )

abnormal lung morphology ( J:44108 )

pulmonary vascular congestion ( J:44108 )

• mutant lungs exhibit congestion of pulmonary septal capillaries

increased lung weight ( J:44108 )

• homozygotes exhibit a higher lung-to-body-weight ratio relative to wild-type mice

pulmonary edema ( J:44108 )

immune system

lymphangiectasis ( J:44108 )

• homozygotes display dilated perivascular lymphatics

liver/biliary system

liver vascular congestion ( J:44108 )

• in a number of homozygotes that die at >24 h after birth, mutant livers display changes compatible with passive congestion

• such changes are suggestive of acute ischemia secondary to heart failure

macrovesicular hepatic steatosis ( J:44108 )

• in a number of homozygotes dying at >24 h after birth, mutant livers contain macrovesicular lipid deposits

microvesicular hepatic steatosis ( J:44108 )

• in a number of homozygotes dying at >24 h after birth, mutant livers contain microvesicular lipid deposits

homeostasis/metabolism

pulmonary edema ( J:44108 )

cellular

patent ductus arteriosus ( J:44108 )

• although the DA appears constricted relative to the fetal DA at 3 hrs after birth, homozygous newborns exhibit obvious patency of the DA at both 7 and 12 hrs after birth

• at 12 hrs, swelling of the intima absent and the endothelium remains a single layer of cells contiguous with that of the aorta

Genotype
MGI:3590045

hm2

• Allelic Composition: Ptger4^tm1Bhk/Ptger4^tm1Bhk
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6 * DBA/2

mortality/aging

mortality/aging ( J:44108 )

N • only 5% of homozygotes survive on a mixed genetic background; selective breeding of these mice results in a 21% survival rate

cardiovascular system

abnormal vascular regression ( J:44108 )

• at 9 weeks, all surviving homozygotes exhibit closure of the ductus arteriosus and appear healthy; however, closure is restricted to the region of the DA immediately adjacent to the pulmonary trunk, resulting in a funnel-shaped diverticulum that remains open at the aortic end

• notably, indomethacin fails to induce DA closure in homozgous mutant fetuses

immune system

immune system phenotype ( J:78964 )

N • at 8-10 weeks, surviving homozygotes show no significant changes in lymphocyte, monocyte, neutrophil, basophil, or eosinophil counts relative to wild-type mice

abnormal macrophage physiology ( J:78964 )

• after CAIA induction, peritoneal macrophages from diseased homozygotes release less IL-6 than wild-type mice under baseline conditions; however, no difference in IL-6 levels is noted after stimulation with LPS

abnormal circulating serum amyloid protein level ( J:78964 )

• after CAIA induction, diseased homozygotes display serum amyloid A levels comparable to those observed in non-diseased homozygotes

abnormal cytokine level ( J:78964 )

• after CAIA induction, diseased mutant livers exhibit significantly reduced IL-1beta levels relative to wild-type livers

abnormal circulating interleukin-6 level ( J:78964 )

• after CAIA induction, diseased homozygotes display an attenuated increase in serum and peritoneal exudate IL-6 levels relative to wild-type mice

decreased susceptibility to induced arthritis ( J:78964 )

• homozygotes exhibit a significant reduction in both severity and incidence of collagen antibody-induced rheumatoid arthritis (CAIA) relative to wild-type controls, based on paw swelling/redness and joint ankylosis

rheumatoid arthritis ( J:78964 )

• in the CAIA model, 8 of 24 homozygotes develop arthritis with significantly fewer severely arthritic joints than wild-type mice

• stifle joints exhibit reduced bone damage, proteoglycan loss, and type II collagen breakdown, consistent with attenuated clinical signs

skeleton

decreased susceptibility to induced arthritis ( J:78964 )

• homozygotes exhibit a significant reduction in both severity and incidence of collagen antibody-induced rheumatoid arthritis (CAIA) relative to wild-type controls, based on paw swelling/redness and joint ankylosis

rheumatoid arthritis ( J:78964 )

• in the CAIA model, 8 of 24 homozygotes develop arthritis with significantly fewer severely arthritic joints than wild-type mice

• stifle joints exhibit reduced bone damage, proteoglycan loss, and type II collagen breakdown, consistent with attenuated clinical signs

homeostasis/metabolism

abnormal circulating serum amyloid protein level ( J:78964 )

• after CAIA induction, diseased homozygotes display serum amyloid A levels comparable to those observed in non-diseased homozygotes

abnormal prostaglandin level ( J:78964 )

• after CAIA induction, diseased homozygotes display an attenuated increase in peritoneal exudate PGE2 levels relative to wild-type mice

abnormal cytokine level ( J:78964 )

• after CAIA induction, diseased mutant livers exhibit significantly reduced IL-1beta levels relative to wild-type livers

abnormal circulating interleukin-6 level ( J:78964 )

• after CAIA induction, diseased homozygotes display an attenuated increase in serum and peritoneal exudate IL-6 levels relative to wild-type mice

hematopoietic system

abnormal macrophage physiology ( J:78964 )

• after CAIA induction, peritoneal macrophages from diseased homozygotes release less IL-6 than wild-type mice under baseline conditions; however, no difference in IL-6 levels is noted after stimulation with LPS

cellular

abnormal vascular regression ( J:44108 )

• at 9 weeks, all surviving homozygotes exhibit closure of the ductus arteriosus and appear healthy; however, closure is restricted to the region of the DA immediately adjacent to the pulmonary trunk, resulting in a funnel-shaped diverticulum that remains open at the aortic end

• notably, indomethacin fails to induce DA closure in homozgous mutant fetuses