Phenotypes associated with this allele

• Allele Symbol: Mapk14^tm1Nbr
• Allele Name: targeted mutation 1, Angel R Nebreda
• Allele ID: MGI:2177831
• Summary: 3 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Mapk14^tm1Nbr/Mapk14^tm1Nbr	either: (involves: 129S/SvEv * 129S1/Sv * 129X1/SvJ * C57BL/6) or (involves: 129S/SvEv * 129S1/Sv * 129X1/SvJ * C57BL/6 * CD-1)	MGI:3663732
cn2	Mapk14^tm1Nbr/Mapk14^tm2Nbr Polr2a^tm1(cre/ERT2)Bbd/Polr2a^+	involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * CD-1 * SJL	MGI:3716854
cn3	Kras^tm1Bbd/Kras^+ Mapk14^tm1Nbr/Mapk14^tm2Nbr Polr2a^tm1(cre/ERT2)Bbd/Polr2a^+	involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * CD-1 * SJL	MGI:3716855

Genotype
MGI:3663732

hm1

• Allelic Composition: Mapk14^tm1Nbr/Mapk14^tm1Nbr
• Genetic Background: either: (involves: 129S/SvEv * 129S1/Sv * 129X1/SvJ * C57BL/6) or (involves: 129S/SvEv * 129S1/Sv * 129X1/SvJ * C57BL/6 * CD-1)

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

mortality/aging

embryonic lethality during organogenesis, complete penetrance ( J:63877 )

• homozygotes die at around midgestation, with most embryos appearing moribund or undergoing resorption at E11.5; no homozygotes are recovered after E12.5

• notably, tetraploid-rescued embryos develop to term with a normal cardiovascular system, indicating that the cardiac defect noted at E10.5 is secondary to aberrant placental development

embryo

abnormal placenta vasculature ( J:63877 )

• mutant embryonic blood vessels are often dilated and appear to be trapped in superficial layers of the placenta, failing to penetrate deeper into the labyrinthine layer

abnormal placental labyrinth vasculature morphology ( J:63877 )

• at E10.5, homozygotes display an almost complete absence of intermingling of maternal and embryonic blood vessels

increased embryonic tissue cell apoptosis ( J:63877 )

• at E10.5, large clusters of TUNEL-positive cells are found in sections of the neural tube and dorsal regions of the embryo, suggesting inadequate oxygen/nutrient supply

embryonic growth retardation ( J:63877 )

• Background Sensitivity: at E10.5, homozygotes of mixed genetic backgrounds display mild growth retardation; however, severity is significantly increased after backcrossing to C57BL/6 mice

• tetraploid-rescued embryos exhibit normal growth development at E12.5-E18.5

abnormal placenta labyrinth morphology ( J:63877 )

• at E10.5, the size of the mutant placental labyrinthine layer is severely reduced

abnormal trophoblast layer morphology ( J:63877 )

• at E10.5, the mutant labyrinthine trophoblast layer close to the chorionic plate is significantly thickened

pale yolk sac ( J:63877 )

• at E10.5, mutant yolk sacs are sometimes pale

abnormal placenta development ( J:63877 )

• at E10.5, homozygotes show abnormal placental layering, resulting in poor oxygen/nutrient transfer across the placenta

impaired placental function ( J:63877 )

• at E10.5

growth/size/body

embryonic growth retardation ( J:63877 )

• Background Sensitivity: at E10.5, homozygotes of mixed genetic backgrounds display mild growth retardation; however, severity is significantly increased after backcrossing to C57BL/6 mice

• tetraploid-rescued embryos exhibit normal growth development at E12.5-E18.5

cardiovascular system

abnormal cranial blood vasculature morphology ( J:63877 )

• at E10.5, homozygotes display a reduced head vasculature with absence of large vessels while the majority of blood vessels in the embryo proper and yolk sac remain unaffected

• tetraploid-rescued embryos exhibit normal head vasculature

abnormal placenta vasculature ( J:63877 )

• mutant embryonic blood vessels are often dilated and appear to be trapped in superficial layers of the placenta, failing to penetrate deeper into the labyrinthine layer

abnormal placental labyrinth vasculature morphology ( J:63877 )

• at E10.5, homozygotes display an almost complete absence of intermingling of maternal and embryonic blood vessels

absent myocardial trabeculae ( J:63877 )

• at E10.5, myocardial trabeculation is almost absent

thin myocardium ( J:63877 )

• at E10.5, the mutant heart wall is very thin

decreased fetal cardiomyocyte number ( J:63877 )

• at E10.5, mutant myocardial cells are largely absent; however, no significant changes in cardiomyocyte proliferation or apoptosis are observed at E9.5 or E10.5

• tetraploid-rescued embryos exhibit a normal myocardium, indicating that myocardial cell loss is a consequence of placental dysfunction

poor circulation ( J:63877 )

• at E10.5, all mutant embryos show insufficient blood circulation

decreased cardiac muscle contractility ( J:63877 )

• at E10.5, all homozygotes have beating hearts but exhibit weaker contractions

cellular

increased embryonic tissue cell apoptosis ( J:63877 )

• at E10.5, large clusters of TUNEL-positive cells are found in sections of the neural tube and dorsal regions of the embryo, suggesting inadequate oxygen/nutrient supply

muscle

absent myocardial trabeculae ( J:63877 )

• at E10.5, myocardial trabeculation is almost absent

thin myocardium ( J:63877 )

• at E10.5, the mutant heart wall is very thin

decreased cardiac muscle contractility ( J:63877 )

• at E10.5, all homozygotes have beating hearts but exhibit weaker contractions

integument

pallor ( J:63877 )

• at E10.5, homozygous mutant embryos appear sometimes pale

Genotype
MGI:3716854

cn2

• Allelic Composition: Mapk14^tm1Nbr/Mapk14^tm2Nbr; Polr2a^{tm1(cre/ERT2)Bbd}/Polr2a⁺
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * CD-1 * SJL

mortality/aging

premature death ( J:122397 )

• mice die before week 32 due to increased lung cancer progression

respiratory system

enlarged lung ( J:122397 )

• 20 weeks after treatment, lungs are increased in size

increased lung tumor incidence ( J:122397 )

• 2 weeks after 5-hydroxytamoxifen treatment, small tumors are found in the lungs

• 20 weeks after treatment, lungs are oversized with 2-3 times as many tumors, many often >2mm in diameter, while lungs of Kras, Mapk14 heterozygotes have normal lungs with fewer, smaller tumors; tumors in Mapk14 homozygotes are more poorly differentiated and have higher mitotic indices

• at 26 weeks, total tumor number is slightly higher than in controls with much higher numbers of tumors larger than 2 mm in diameter and a higher ratio of lung mass to total mass

increased lung adenoma incidence ( J:122397 )

• tumors are detected 2 weeks after 5-hydroxytamoxifen treatment and after 4 weeks, clear signs of adenomas are present in most lungs compared to only a few small adenomas in lungs of treated Kras, Mapk14^tm2Nbr/+ control mice

increased lung adenocarcinoma incidence ( J:122397 )

• adenocarcinomas are detected at 15 weeks but not in controls

abnormal lung development ( J:122397 )

• lung differentiation is abnormal with increased SP-C-positive cells

neoplasm

abnormal tumor incidence ( J:122397 )

• mice also have tumors in the thymus and organs such as kidney and liver by 24 weeks after treatment whereas controls only have tumors in lungs and thymus

increased lung tumor incidence ( J:122397 )

• 2 weeks after 5-hydroxytamoxifen treatment, small tumors are found in the lungs

• 20 weeks after treatment, lungs are oversized with 2-3 times as many tumors, many often >2mm in diameter, while lungs of Kras, Mapk14 heterozygotes have normal lungs with fewer, smaller tumors; tumors in Mapk14 homozygotes are more poorly differentiated and have higher mitotic indices

• at 26 weeks, total tumor number is slightly higher than in controls with much higher numbers of tumors larger than 2 mm in diameter and a higher ratio of lung mass to total mass

increased lung adenoma incidence ( J:122397 )

• tumors are detected 2 weeks after 5-hydroxytamoxifen treatment and after 4 weeks, clear signs of adenomas are present in most lungs compared to only a few small adenomas in lungs of treated Kras, Mapk14^tm2Nbr/+ control mice

increased lung adenocarcinoma incidence ( J:122397 )

• adenocarcinomas are detected at 15 weeks but not in controls

growth/size/body

enlarged lung ( J:122397 )

• 20 weeks after treatment, lungs are increased in size

Genotype
MGI:3716855

cn3

• Allelic Composition: Kras^tm1Bbd/Kras⁺; Mapk14^tm1Nbr/Mapk14^tm2Nbr; Polr2a^{tm1(cre/ERT2)Bbd}/Polr2a⁺
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * CD-1 * SJL

mortality/aging

premature death ( J:122397 )

• mice die before week 32 due to increased lung cancer progression

respiratory system

enlarged lung ( J:122397 )

• 20 weeks after treatment, lungs are increased in size

increased lung tumor incidence ( J:122397 )

• 2 weeks after 5-hydroxytamoxifen treatment, small tumors are found in the lungs

• 20 weeks after treatment, lungs are oversized with 2-3 times as many tumors, many often >2mm in diameter, while lungs of Kras, Mapk14 heterozygotes have normal lungs with fewer, smaller tumors; tumors in Mapk14 homozygotes are more poorly differentiated and have higher mitotic indices

• at 26 weeks, total tumor number is slightly higher than in controls with much higher numbers of tumors larger than 2 mm in diameter and a higher ratio of lung mass to total mass

increased lung adenoma incidence ( J:122397 )

• tumors are detected 2 weeks after 5-hydroxytamoxifen treatment and after 4 weeks, clear signs of adenomas are present in most lungs compared to only a few small adenomas in lungs of treated Kras, Mapk14^tm2Nbr/+ control mice

increased lung adenocarcinoma incidence ( J:122397 )

• adenocarcinomas are detected at 15 weeks but not in controls

abnormal lung development ( J:122397 )

• lung differentiation is abnormal with increased SP-C-positive cells

neoplasm

abnormal tumor incidence ( J:122397 )

• mice also have tumors in the thymus and organs such as kidney and liver by 24 weeks after treatment whereas controls only have tumors in lungs and thymus

increased lung tumor incidence ( J:122397 )

• 2 weeks after 5-hydroxytamoxifen treatment, small tumors are found in the lungs

• 20 weeks after treatment, lungs are oversized with 2-3 times as many tumors, many often >2mm in diameter, while lungs of Kras, Mapk14 heterozygotes have normal lungs with fewer, smaller tumors; tumors in Mapk14 homozygotes are more poorly differentiated and have higher mitotic indices

• at 26 weeks, total tumor number is slightly higher than in controls with much higher numbers of tumors larger than 2 mm in diameter and a higher ratio of lung mass to total mass

increased lung adenoma incidence ( J:122397 )

• tumors are detected 2 weeks after 5-hydroxytamoxifen treatment and after 4 weeks, clear signs of adenomas are present in most lungs compared to only a few small adenomas in lungs of treated Kras, Mapk14^tm2Nbr/+ control mice

increased lung adenocarcinoma incidence ( J:122397 )

• adenocarcinomas are detected at 15 weeks but not in controls

growth/size/body

enlarged lung ( J:122397 )

• 20 weeks after treatment, lungs are increased in size