Phenotypes associated with this allele

• Allele Symbol: Foxa2^tm1Khk
• Allele Name: targeted mutation 1, Klaus H Kaestner
• Allele ID: MGI:2177337
• Summary: 12 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Foxa2^tm1Khk/Foxa2^tm1Khk	involves: 129P2/OlaHsd * CD-1	MGI:2177357
cn2	Foxa2^tm1Khk/Foxa2^tm1Khk	involves: 129P2/OlaHsd * C57BL/6 * CD-1 * DBA	MGI:2177372
cn3	Foxa2^tm1Khk/Foxa2^tm1Khk Tg(SFTPC-rtTA)5Jaw/0 Tg(tetO-cre)1Jaw/0	involves: 129 * 129P2/OlaHsd * C57BL/6	MGI:3036449
cn4	Foxa1^tm1Khk/Foxa1^+ Foxa2^tm1Khk/Foxa2^tm1Khk Tg(Pdx1-cre)6Cvw/0	involves: 129 * C57BL/6 * CBA * SJL	MGI:3831162
cn5	Foxa1^tm1Khk/Foxa1^tm1Khk Foxa2^tm1Khk/Foxa2^+ Tg(Pdx1-cre)6Cvw/0	involves: 129 * C57BL/6 * CBA * SJL	MGI:3831161
cn6	Foxa1^tm1Khk/Foxa1^tm1Khk Foxa2^tm1Khk/Foxa2^tm1Khk Tg(Pdx1-cre)6Cvw/0	involves: 129 * C57BL/6 * CBA * SJL	MGI:3831163
cn7	Foxa2^tm1Khk/Foxa2^tm1Khk Pgr^tm2(cre)Lyd/Pgr^+	involves: 129P2/OlaHsd * 129S1/Sv * 129X1/SvJ * C57BL/6	MGI:6854709
cn8	Foxa1^tm1Khk/Foxa1^tm1Khk Foxa2^tm1Khk/Foxa2^tm1Khk Tg(Alb1-cre)1Khk/0	involves: 129P2/OlaHsd * 129S1/Sv * 129X1/SvJ * C57BL/6 * SJL	MGI:5314251
cn9	Foxa2^tm1Jrt/Foxa2^tm1Khk Tg(Nes-cre)1Wme/0	involves: 129P2/OlaHsd * C57BL/6 * CBA	MGI:3029694
cn10	Foxa2^tm1Khk/Foxa2^tm1Khk Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: 129P2/OlaHsd * C57BL/6 * CD-1 * DBA	MGI:2177363
cn11	Foxa2^tm1Khk/Foxa2^tm1Khk Tg(Foxa3-cre)1Khk/0	involves: 129P2/OlaHsd * C57BL/6 * CD-1 * DBA	MGI:3700827
cn12	Foxa2^tm1Khk/Foxa2^tm1Khk Tg(Scgb1a1-rtTA)1Jaw/0 Tg(tetO-cre)1Jaw/0	Not Specified	MGI:3036450

Genotype
MGI:2177357

hm1

• Allelic Composition: Foxa2^tm1Khk/Foxa2^tm1Khk
• Genetic Background: involves: 129P2/OlaHsd * CD-1

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

normal phenotype

no abnormal phenotype detected ( J:63039 )

• homozygous mice exhibit no discernable phenotype; mice are viable and fertile

Genotype
MGI:2177372

cn2

• Allelic Composition: Foxa2^tm1Khk/Foxa2^tm1Khk
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6 * CD-1 * DBA

mortality/aging

postnatal lethality, complete penetrance ( J:70409 )

• mutant animals die between P9 and P12

behavior/neurological

seizures ( J:70409 )

endocrine/exocrine glands

abnormal pancreatic beta cell morphology ( J:70409 )

• pancreatic beta cells are present, but have abnormal morphology

disorganized pancreatic islets ( J:70409 )

• disorganized morphology with non-beta cells present in the core

abnormal insulin secretion ( J:70409 )

• beta cells exhibit dysregulated insulin secretion

growth/size/body

postnatal growth retardation ( J:70409 )

• mutant animals are smaller than controls at P8

homeostasis/metabolism

abnormal insulin secretion ( J:70409 )

• beta cells exhibit dysregulated insulin secretion

hypoglycemia ( J:70409 )

• described as severe in mutant animals

decreased circulating glucagon level ( J:70409 )

• level was 5 fold less in mutant mice than in control animals

increased circulating insulin level ( J:70409 )

• the plasma insulin level was very high considering the low glucose levels in mutant animals

increased glycogen level ( J:70409 )

• mutant mice have a 2.5-fold higher glycogen content than controls

nervous system

seizures ( J:70409 )

Genotype
MGI:3036449

cn3

• Allelic Composition: Foxa2^tm1Khk/Foxa2^tm1Khk; Tg(SFTPC-rtTA)5Jaw/0; Tg(tetO-cre)1Jaw/0
• Genetic Background: involves: 129 * 129P2/OlaHsd * C57BL/6

mortality/aging

neonatal lethality, incomplete penetrance ( J:93473 )

• most mice treated with doxycycline from E0 die on P1

postnatal lethality, incomplete penetrance ( J:88601 , J:93473 )

• 50% of mice treated with doxycycline from E0 through P16 died within 30 days of birth (J:88601)

• only 46% of mice treated with doxycycline from E0 survive to P5 (J:93473)

hematopoietic system

increased neutrophil cell number ( J:88601 )

• observed in bronchoalveolar lavage from mice treated with doxycycline from E0 through P16

increased macrophage cell number ( J:88601 )

• observed in bronchoalveolar lavage from mice treated with doxycycline from E0 through P16

immune system

increased neutrophil cell number ( J:88601 )

• observed in bronchoalveolar lavage from mice treated with doxycycline from E0 through P16

increased macrophage cell number ( J:88601 )

• observed in bronchoalveolar lavage from mice treated with doxycycline from E0 through P16

respiratory system

pulmonary vascular congestion ( J:93473 )

• mice treated with doxycycline from E0 and found to be in distress or moribund on P1 display pulmonary congestion

impaired lung alveolus development ( J:88601 , J:93473 )

• impaired alveogenesis marked by fewer peripheral lung saccules and decreased alveolar septation; apparent at 3 days of age in mice treated with doxycycline from E0 through P16 (J:88601)

abnormal lung saccule morphology ( J:93473 )

• at E18.5, mice treated with doxycycline from E0 display immature peripheral lung saccules, resembling those normally seen at E16-E17

abnormal pulmonary alveolus epithelial cell morphology ( J:93473 )

• at E18.5, squamous type I cells are missing, alveolar walls are thickened and lined by immature cuboidal type II cells, cytoplasmic glycogen is dispersed, and apical microvilli are absent

• however, no evidence of capillary leakage or endothelial cell abnormalities are observed

absent type I pneumocytes ( J:93473 )

• at E18.5, no squamous type I cells are observed in mice treated with doxycycline from E0

abnormal type II pneumocyte morphology ( J:93473 )

• at E18.5, mice treated with doxycycline from E0 show absence of lamellar bodies in alveolar type II cells

absent alveolar lamellar bodies ( J:93473 )

increased pulmonary alveolus wall thickness ( J:93473 )

• at E18.5, mice treated with doxycycline from E0 show thickened alveolar walls lined by immature cuboidal type II cells

atelectasis ( J:93473 )

• mice treated with doxycycline from E0 and found to be in distress or moribund on P1 display focal or extensive atelectasis

dilated respiratory conducting tube ( J:88601 )

• increased airspace in mice prenatally treated with doxycycline

• postnatal treatment with doxycycline also resulted in increased airspace but to a lesser extent

• normal prenatal lung morphogenesis

pulmonary hyaline membrane formation ( J:93473 )

• mice treated with doxycycline from E0 and found to be in distress or moribund on P1 display hyaline membrane formation

increased respiratory mucosa goblet cell number ( J:88601 )

• goblet cell hyperplasia, associated with the accumulation of both neutral and acidic mucins, observed in mice treated with doxycycline from E0 through P16

respiratory distress ( J:93473 )

• ~50% of mice treated with doxycycline from E0 develop severe respiratory distress within 2-3 hrs of birth

abnormal surfactant composition ( J:93473 )

• at E18.5, the fractional content of phosphatidylcholine (PC) and saturated PC are markdely reduced, whereas that of phosphatidylethanolamine, sphingomyelin, and phosphatidylserine is increased in the lungs of mice treated with doxycycline from E0

abnormal surfactant secretion ( J:93473 )

• SP-A, SP-B, and SP-C mRNAs are significantly decreased at E18.5

• the active SP-B peptide is markedly decreased in lung homogenates prior to birth

• SP-D mRNAs are significantly increased at E18.5

decreased surfactant secretion ( J:93473 )

• at E18.5, no secreted surfactant is detected in the air spaces of mice treated with doxycycline from E0

homeostasis/metabolism

cyanosis ( J:93473 )

• ~50% of mice treated with doxycycline from E0 display cyanosis

behavior/neurological

pup cannibalization ( J:93473 )

♀ • newborn mice are frequently cannibalized by the mother

cardiovascular system

pulmonary vascular congestion ( J:93473 )

• mice treated with doxycycline from E0 and found to be in distress or moribund on P1 display pulmonary congestion

Genotype
MGI:3831162

cn4

• Allelic Composition: Foxa1^tm1Khk/Foxa1⁺; Foxa2^tm1Khk/Foxa2^tm1Khk; Tg(Pdx1-cre)6Cvw/0
• Genetic Background: involves: 129 * C57BL/6 * CBA * SJL

mortality/aging

postnatal lethality, complete penetrance ( J:143476 )

• mice die prior to P5

endocrine/exocrine glands

decreased pancreatic beta cell number ( J:143476 )

pancreatic islet hypoplasia ( J:143476 )

pancreas hypoplasia ( J:143476 )

• the pancreas occupies 31% relative area compared to in wild-type mice

exocrine pancreas hypoplasia ( J:143476 )

digestive/alimentary system

exocrine pancreas hypoplasia ( J:143476 )

Genotype
MGI:3831161

cn5

• Allelic Composition: Foxa1^tm1Khk/Foxa1^tm1Khk; Foxa2^tm1Khk/Foxa2⁺; Tg(Pdx1-cre)6Cvw/0
• Genetic Background: involves: 129 * C57BL/6 * CBA * SJL

endocrine/exocrine glands

endocrine/exocrine gland phenotype ( J:143476 )

N • unlike in mice lacking both alleles of Fox2a, pancreatic development is normal

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:143476 )

N • mice are euglycemic

Genotype
MGI:3831163

cn6

• Allelic Composition: Foxa1^tm1Khk/Foxa1^tm1Khk; Foxa2^tm1Khk/Foxa2^tm1Khk; Tg(Pdx1-cre)6Cvw/0
• Genetic Background: involves: 129 * C57BL/6 * CBA * SJL

mortality/aging

postnatal lethality, complete penetrance ( J:143476 )

• mice die within 2 days of birth

endocrine/exocrine glands

abnormal pancreas morphology ( J:143476 )

• the spaces between the remaining ductal epithelia are filled with stromal tissue, including fibroblasts and smooth musce cells

decreased pancreatic beta cell number ( J:143476 )

• very few beta cells are present between E17.5 and P1

pancreatic islet hypoplasia ( J:143476 )

abnormal pancreas development ( J:143476 )

• at E13.5, pancreatic precursor cells fail to expand resulting in fewer than normal glucagon+ and amylase+ cells

• pancreatic development is arrested at the early pancreatic cord stage

pancreas hypoplasia ( J:143476 )

• the pancreas occupies 19% relative area compared to in wild-type mice

• the numbers of endocrine cells, exocrine cells, and total epithelial tissue is severely decreased compared to in wild-type mice with remaining cells exhibiting an almost exclusively ductal phenotype

exocrine pancreas hypoplasia ( J:143476 )

homeostasis/metabolism

hyperglycemia ( J:143476 )

digestive/alimentary system

exocrine pancreas hypoplasia ( J:143476 )

Genotype
MGI:6854709

cn7

• Allelic Composition: Foxa2^tm1Khk/Foxa2^tm1Khk; Pgr^tm2(cre)Lyd/Pgr⁺
• Genetic Background: involves: 129P2/OlaHsd * 129S1/Sv * 129X1/SvJ * C57BL/6

reproductive system

abnormal decidualization ( J:165229 )

♀ • although blastocysts can attach to the uterine lumen and initiate a decidual response, the decidual region and size of the embryos is significantly smaller on day 5.5 of natural pregnancy

♀ • after induction of artificial decidualization, stimulated horn weight:unstimulated horn weight ratio is significantly lower than that in controls

♀ • decidualization defect can be partially rescued by intrauterine injection of recombinant leukemia inhibitory factor (LIF) prior to the initiation of the decidual response

abnormal endometrial gland development ( J:165229 )

♀ • uteri of 8-wk-old females show a severe defect in endometrial gland development

♀ • loss of endometrial glands results in a marked reduction of leukemia inhibitory factor (Lif) expression on day 3.5 of pseudopregnancy

decreased endometrial gland number ( J:165229 )

♀ • nonpregnant uteri of 8-wk-old females show a severe reduction in the number of endometrial glands relative to control uteri

abnormal embryo invasion ( J:165229 )

♀ • on day 5.5 of pregnancy, embryos fail to exhibit invasion into the uterine stroma through the epithelium

impaired embryo implantation ( J:165229 )

♀ • on day 5.5 of pregnancy, the number of implantation sites is significantly lower than that in control uteri

abnormal uterus physiology ( J:165229 )

♀ • uterus is unable to support embryo invasion and undergo an experimentally induced decidual response with exogenous steroid hormones

reduced female fertility ( J:165229 )

♀ • when mated to wild-type males for a period of 6 months, females exhibit severe subfertility, with significantly fewer litters, pups per litter and total pups born relative to control females

decreased litter size ( J:165229 )

♀ • females produce significantly fewer pups per litter than control females

embryo

abnormal decidualization ( J:165229 )

♀ • although blastocysts can attach to the uterine lumen and initiate a decidual response, the decidual region and size of the embryos is significantly smaller on day 5.5 of natural pregnancy

♀ • after induction of artificial decidualization, stimulated horn weight:unstimulated horn weight ratio is significantly lower than that in controls

♀ • decidualization defect can be partially rescued by intrauterine injection of recombinant leukemia inhibitory factor (LIF) prior to the initiation of the decidual response

endocrine/exocrine glands

abnormal endometrial gland development ( J:165229 )

♀ • uteri of 8-wk-old females show a severe defect in endometrial gland development

♀ • loss of endometrial glands results in a marked reduction of leukemia inhibitory factor (Lif) expression on day 3.5 of pseudopregnancy

decreased endometrial gland number ( J:165229 )

♀ • nonpregnant uteri of 8-wk-old females show a severe reduction in the number of endometrial glands relative to control uteri

Genotype
MGI:5314251

cn8

• Allelic Composition: Foxa1^tm1Khk/Foxa1^tm1Khk; Foxa2^tm1Khk/Foxa2^tm1Khk; Tg(Alb1-cre)1Khk/0
• Genetic Background: involves: 129P2/OlaHsd * 129S1/Sv * 129X1/SvJ * C57BL/6 * SJL

neoplasm

decreased incidence of tumors by chemical induction ( J:181296 )

• male mutants injected with DEN followed by TCPOBOP (carcinogen treatment) show reduced tumor growth compared to control males that develop severe hepatocellular carcinoma

increased incidence of tumors by chemical induction ( J:181296 )

• female mutants injected with DEN followed by TCPOBOP (carcinogen treatment) to induce rapid hepatocellular carcinoma formation, develop multiple and large liver tumors unlike control females that are resistant to hepatocellular carcinoma development

• in females treated with fulverstrant to block estrogen signaling, DEN-induced liver injury is significantly attenuated

• estrogen treatment of male mutants enhances liver injury in DEN-treated males while in DEN-treated controls estrogen treatment prevents liver injury and carcinogenesis

increased hepatocellular carcinoma incidence ( J:181296 )

• female mutants injected with N,N-diethylnitrosamine (DEN) followed by TCPOBOP two-step strategy (carcinogen treatment) to induce rapid hepatocellular carcinoma formation, develop multiple and large liver tumors unlike control females that are resistant to hepatocellular carcinoma development

• male mutants injected with DEN followed by TCPOBOP show reduced tumor growth compared to control males that develop severe hepatocellular carcinoma

homeostasis/metabolism

decreased incidence of tumors by chemical induction ( J:181296 )

• male mutants injected with DEN followed by TCPOBOP (carcinogen treatment) show reduced tumor growth compared to control males that develop severe hepatocellular carcinoma

increased incidence of tumors by chemical induction ( J:181296 )

• female mutants injected with DEN followed by TCPOBOP (carcinogen treatment) to induce rapid hepatocellular carcinoma formation, develop multiple and large liver tumors unlike control females that are resistant to hepatocellular carcinoma development

• in females treated with fulverstrant to block estrogen signaling, DEN-induced liver injury is significantly attenuated

• estrogen treatment of male mutants enhances liver injury in DEN-treated males while in DEN-treated controls estrogen treatment prevents liver injury and carcinogenesis

liver/biliary system

increased hepatocellular carcinoma incidence ( J:181296 )

• female mutants injected with N,N-diethylnitrosamine (DEN) followed by TCPOBOP two-step strategy (carcinogen treatment) to induce rapid hepatocellular carcinoma formation, develop multiple and large liver tumors unlike control females that are resistant to hepatocellular carcinoma development

• male mutants injected with DEN followed by TCPOBOP show reduced tumor growth compared to control males that develop severe hepatocellular carcinoma

Genotype
MGI:3029694

cn9

• Allelic Composition: Foxa2^tm1Jrt/Foxa2^tm1Khk; Tg(Nes-cre)1Wme/0
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6 * CBA

mortality/aging

embryonic lethality during organogenesis, complete penetrance ( J:75055 )

• mutant embryos die at E11.5

embryo

abnormal mesendoderm development ( J:75055 )

• the axial mesendoderm failed to differentiate; the anterior neural plate and anterior definitive endoderm form, but fail to maintain specification

nervous system

abnormal forebrain morphology ( J:75055 )

• anterior head truncations were noted in mutant animals

Genotype
MGI:2177363

cn10

• Allelic Composition: Foxa2^tm1Khk/Foxa2^tm1Khk; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6 * CD-1 * DBA

normal phenotype

no abnormal phenotype detected ( J:63039 )

• homozygous mice exhibit no discernable phenotype; mice are viable and fertile with normal liver metabolism and normal glucose homeostasis

Genotype
MGI:3700827

cn11

• Allelic Composition: Foxa2^tm1Khk/Foxa2^tm1Khk; Tg(Foxa3-cre)1Khk/0
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6 * CD-1 * DBA

mortality/aging

postnatal lethality, complete penetrance ( J:96332 )

• most die by P3, with a few surviving to P5

growth/size/body

decreased body size ( J:96332 )

endocrine/exocrine glands

decreased pancreatic alpha cell number ( J:96332 )

• the number of mature glucagon-positive pancreatic alpha-cells is reduced

disorganized pancreatic islets ( J:96332 )

• islets are irregularly shaped and display a disorganized architecture with many small clusters of endocrine cells embedded in the exocrine tissue

homeostasis/metabolism

hypoglycemia ( J:96332 )

• severely hypoglycemic

decreased circulating glucagon level ( J:96332 )

• 50% reduction of plasma glucagon

integument

decreased skin turgor ( J:96332 )

Genotype
MGI:3036450

cn12

• Allelic Composition: Foxa2^tm1Khk/Foxa2^tm1Khk; Tg(Scgb1a1-rtTA)1Jaw/0; Tg(tetO-cre)1Jaw/0
• Genetic Background: Not Specified

immune system

immune system phenotype ( J:88601 )

N • no increase in the number of neutrophils or macrophages in mice treated with doxycycline from E0 through P16

respiratory system

increased respiratory mucosa goblet cell number ( J:88601 )

• goblet cell hyperplasia, associated with the accumulation of both neutral and acidic mucins, in the larger airways of mice treated with doxycycline from E0 through P16

• neither airspace nor alveolar morphological abnormalities were detected

abnormal respiratory mechanics ( J:88601 )

increased airway resistance ( J:88601 )

• increased in mice treated with doxycycline

decreased lung compliance ( J:88601 )

• decreased in mice treated with doxycycline