Phenotypes associated with this allele

• Allele Symbol: Klf5^tm1Jaw
• Allele Name: targeted mutation 1, Jeffrey A Whitsett
• Allele ID: MGI:3806635
• Summary: 4 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cn1	Klf5^tm1Jaw/Klf5^tm1Jaw Tg(SFTPC-rtTA)5Jaw/0 Tg(tetO-cre)1Jaw/0	involves: 129 * C57BL/6	MGI:3806650
cn2	Klf5^tm1Jaw/Klf5^tm1Jaw Pgr^tm2(cre)Lyd/Pgr^+	involves: 129S1/Sv * 129X1/SvJ	MGI:6870538
cn3	Klf4^tm1Khk/Klf4^tm1Khk Klf5^tm1Jaw/Klf5^tm1Jaw Tg(Pax6-cre,GFP)1Pgr/0	involves: 129S6/SvEvTac * FVB	MGI:5644970
cn4	Klf5^tm1Jaw/Klf5^tm1Jaw Tg(Pax6-cre,GFP)1Pgr/0	involves: FVB	MGI:5644968

Genotype
MGI:3806650

cn1

• Allelic Composition: Klf5^tm1Jaw/Klf5^tm1Jaw; Tg(SFTPC-rtTA)5Jaw/0; Tg(tetO-cre)1Jaw/0
• Genetic Background: involves: 129 * C57BL/6

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

mortality/aging

neonatal lethality, complete penetrance ( J:138576 )

• doxycycline treated mice die shortly after birth due to respiratory distress

respiratory system

abnormal lung development ( J:138576 )

• in doxycycline treated mice, pulmonary mesenchyme is thickened and blood vessels are not found in close proximity to epithelial cells unlike in wild-type mice

• in doxycycline treated mice, lung maturation during saccule development is inhibited

• however, at E15.5 lung development is normal

abnormal lung saccule morphology ( J:138576 )

• at birth, doxycycline treated mice exhibit hypercellular alveolar saccules without the dilated peripheral saccules found in wild-type mice

• saccules in doxycycline treated mice are thickened compared to in wild-type mice

thick lung-associated mesenchyme ( J:138576 )

• doxycycline treated mice exhibit thickened lung mesenchyme

abnormal pulmonary alveolus morphology ( J:138576 )

• at birth, doxycycline treated mice exhibit a decrease in alveolar luminal area compared to wild-type mice

abnormal type I pneumocyte morphology ( J:138576 )

• at birth, doxycycline treated mice exhibit a decrease in squamous epithelial cells compared to in wild-type mice indicating a lack of alveolar type I cell differentiation

• however, pulmonary epithelial cell proliferation following dooxycycline treatment is normal

decreased type I pneumocyte number ( J:138576 )

• at birth, doxycycline treated mice exhibit a decrease in squamous epithelial cells compared to in wild-type mice

abnormal type II pneumocyte morphology ( J:138576 )

• in doxycycline treated mice, type II cells lack lamellar structures found in wild-type cells

absent alveolar lamellar bodies ( J:138576 )

respiratory distress ( J:138576 )

• doxycycline treated mice die shortly after birth due to respiratory distress

abnormal surfactant secretion ( J:138576 )

• unlike in wild-type mice, no surfactant secretion or Sftpb protein is detected in doxycycline treated mice

Genotype
MGI:6870538

cn2

• Allelic Composition: Klf5^tm1Jaw/Klf5^tm1Jaw; Pgr^tm2(cre)Lyd/Pgr⁺
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ

reproductive system

abnormal decidualization ( J:179912 )

♀ • although stromal cells were able to initiate decidualization, the decidual response was severely impaired with smaller decidual sizes and no viable embryos present in implantation chambers on day 8 of pregnancy

♀ • after oil-induced artificial decidualization, fold increase in uterine weight of infused-to-non-infused horns was significantly less than that in controls on day 8 of pseudopregnancy

abnormal embryo attachment ( J:179912 )

♀ • on day 5 of pregnancy, COX2 expression was absent in the uterine luminal epithelium but present in stromal cells at the blastocyst site, suggesting that poor embryo attachment might be due to aberrant COX2 expression

failure of embryo implantation ( J:179912 )

♀ • although embryos did develop to blastocysts in uteri, most failed to implant or showed defective implantation

♀ • blastocysts remained entrapped within the luminal epithelium past the window of implantation

impaired embryo implantation ( J:179912 )

♀ • on day 5 of pregnancy, 8 of 11 females exhibited implantation sites but the number of implantation sites per female was significantly lower than that in control females

♀ • on day 6, the uterine luminal epithelium around the implantation chamber failed to degenerate and show loss of E-cadherin, unlike in control uteri

♀ • on day 7, implanted embryos were either very small or absorbed; some embryos were still surrounded by epithelial cells but showed signs of degeneration

♀ • most implantation sites showed continued growth until day 8 but the number of sites on day 8 was similar to that on days 5 and 6

♀ • on day 8, the weight of implantation sites was significantly lower than that in control females

♀ • however, initiation of embryo-uterine interplay was not delayed

abnormal uterine receptivity ( J:179912 )

♀ • uteri are largely unfavorable for normal implantation

♀ • however, uterine responsiveness to estrogen and P4 was normal

female infertility ( J:179912 )

♀ • most females were found to be infertile

reduced female fertility ( J:179912 )

♀ • after mating with wild-type males, only 2 of 10 plug-positive females produced pups

decreased litter size ( J:179912 )

♀ • 2 of 10 plug-positive females tested gave birth to only 2 and 3 pups/litter whereas control females delivered 8 pups/litter

embryo

abnormal decidualization ( J:179912 )

♀ • although stromal cells were able to initiate decidualization, the decidual response was severely impaired with smaller decidual sizes and no viable embryos present in implantation chambers on day 8 of pregnancy

♀ • after oil-induced artificial decidualization, fold increase in uterine weight of infused-to-non-infused horns was significantly less than that in controls on day 8 of pseudopregnancy

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:179912 )

♀N • females show normal serum estrogen (E2) and progesterone (P4) levels on day 4 of pregnancy

Genotype
MGI:5644970

cn3

• Allelic Composition: Klf4^tm1Khk/Klf4^tm1Khk; Klf5^tm1Jaw/Klf5^tm1Jaw; Tg(Pax6-cre,GFP)1Pgr/0
• Genetic Background: involves: 129S6/SvEvTac * FVB

vision/eye

decreased cornea stroma thickness ( J:175263 )

• at 8 weeks of age, the mutant corneal stroma is thinner with relatively fewer keratocytes relative to wild-type and single Klf5 conditional knockout corneas

eyelids fail to open ( J:175263 )

• mutant eyes fail to open as late as 35 weeks after birth, the latest stage examined

abnormal ocular surface morphology ( J:175263 )

• co-ablation of Klf4 and Klf5 in the ocular surface results in more severe eyelid and corneal abnormalities than those in either single conditional knockout

abnormal conjunctival epithelium morphology ( J:175263 )

• at 8 weeks of age, the mutant conjunctival epithelium is thinner than the wild-type or single Klf5 conditional knockout epithelium

absent conjunctiva goblet cells ( J:175263 )

• at 8 weeks of age, conjunctiva goblet cells are missing

abnormal cornea epithelium morphology ( J:175263 )

• at 8 weeks of age, the mutant corneal epithelium is thinner than the wild-type and single Klf5 conditional knockout corneal epithelia, and remains fused to the eyelids

Genotype
MGI:5644968

cn4

• Allelic Composition: Klf5^tm1Jaw/Klf5^tm1Jaw; Tg(Pax6-cre,GFP)1Pgr/0
• Genetic Background: involves: FVB

vision/eye

lacrimal gland inflammation ( J:175263 )

• at 8 weeks of age, mutant lacrimal glands display numerous infiltrating cells, indicating inflammation

abnormal extraocular muscle morphology ( J:175263 )

• at 8 weeks of age, a thicker extra-ocular muscle is observed

abnormal iris morphology ( J:175263 )

• >80% of adult mutant eyes are small and contain a hypertrophic iris

small pupil ( J:175263 )

• >80% of adult mutant eyes exhibit small pupils

anterior iris synechia ( J:175263 )

• frequent iridocorneal fusion is observed

posterior iris synechia ( J:175263 )

• frequent iridolenticular fusion is observed

abnormal cornea morphology ( J:175263 )

• at 8 weeks of age, a rough and translucent cornea is observed

increased cornea thickness ( J:175263 )

• mutant corneas are thicker than wild-type at P6, P11, P21 and at 10 weeks of age

• however, corneas appear normal at E13.5, E15.5 and E18.5

abnormal cornea stroma morphology ( J:175263 )

• mutant corneal stroma is relatively more intensely stained by PAS, suggesting increased levels of proteoglycans

increased cornea stroma thickness ( J:175263 )

• postnatal mutant corneal stroma is hypercellular

• at 8 weeks of age, central corneal stromal thickness and cell density are increased

cornea opacity ( J:175263 )

• at 8 weeks of age

abnormal lens morphology ( J:175263 )

• mutant lenses appear spongy and deformed at P6, P11, P21 and at 10 weeks of age

abnormal lens epithelium morphology ( J:175263 )

• at E18.5 and P1, mutant lenses contain significantly fewer epithelial cells in the central anterior region than wild-type controls

• also, fewer and abnormally arranged nuclei are observed in the differentiating equatorial region

disorganized secondary lens fibers ( J:175263 )

• although mutant primary lens fiber cells appear normal at E13.5 and E15.5, nuclei in E18.5 and P1 lens equatorial regions are disorganized, suggesting defects in secondary fiber formation

small lens ( J:175263 )

• >80% of postnatal mutant lenses are smaller than wild-type

microphthalmia ( J:175263 )

• at 8 weeks of age, the enucleated mutant eyeballs are relatively smaller than wild-type

• small eyes are noted at P6, P11, P21 and at 10 weeks of age

• >80% of adult mutant eyes show a small eye phenotype

• however, early eye development is relatively normal

abnormal eyelid morphology ( J:175263 )

• at P21, mutant eyelashes are irregularly oriented and the surrounding fur is disorganized

• mutant eyelids are swollen and hypercellular and contain fewer irregularly spaced Meibomian gland orifices at the mucocutaneous junction

• the palpebral epidermis is thicker with 7-9 layers of keratinocytes relative to 2-3 in wild-type controls

• mutant eyelids contain significantly enlarged hair follicles and sebaceous glands

• however, no major differences are observed in eyelid morphology at P5, P8 and P11

eyelid edema ( J:175263 )

• mutant eyelids are swollen at P6, P11, P21 and at 10 weeks of age

abnormal Meibomian gland acinus morphology ( J:175263 )

• at P21, mutant Meibomian glands exhibit disorganized, variably sized acini

abnormal Meibomian gland development ( J:175263 )

• a Meibomian gland bud is noted at P6 suggesting timely induction, but appears disorganized; this feature becomes more prominent at P11 and P21

• at P21, the swollen eyelids are hypercellular and contain severely malformed Meibomian glands with disorganized acini

abnormal eyelid aperture ( J:175263 )

• while wild-type eyelids open at P12, mutant eyelids remain closed as late as P21

narrow eye opening ( J:175263 )

• small palpebral fissure at P21

abnormal ocular surface morphology ( J:175263 )

• at P21, mutants display a >2-fold increase in epithelial cell proliferation in the eyelids, cornea, and conjunctiva, as determined by Ki67 staining

• Ki67-positive cells are significantly increased in mutant palpebral epidermis and eyelid hair follicles

• while Ki67-positive cells are restricted to basal epithelia in wild-type controls, they are also found in the spinous cell layers in the mutant cornea and conjunctiva

abnormal lacrimal gland morphology ( J:175263 )

• at 8 weeks of age, mutant lacrimal glands display excessive vasculature and disrupted acinar organization, unlike wild-type controls

lacrimal gland necrosis ( J:175263 )

• at 8 weeks of age, mutant lacrimal glands display interspersed dark spots resembling necrotic spots

abnormal conjunctival epithelium morphology ( J:175263 )

• at P21 and at 10 weeks, the mutant conjunctival epithelium appears rough and discontinuous, indicating a disrupted epithelial barrier

absent conjunctiva goblet cells ( J:175263 )

• at P21 and at 10 weeks, conjunctiva goblet cells are absent, unlike in wild-type controls

abnormal palpebral conjunctiva morphology ( J:175263 )

• at P21, the mutant palpebral conjunctiva is swollen and inflamed (reddish)

decreased cornea epithelium thickness ( J:175263 )

• at P21 and at 10 weeks, the mutant corneal epithelial basement membrane is thin and discontinuous, unlike in wild-type controls

cellular

increased cell proliferation ( J:175263 )

• at P21, mutants display a >2-fold increase in epithelial cell proliferation in the eyelids, cornea, and conjunctiva, as determined by Ki67 staining

• Ki67-positive cells are significantly increased in mutant palpebral epidermis and eyelid hair follicles

• while Ki67-positive cells are restricted to basal epithelia in wild-type controls, they are also found in the spinous cell layers in the mutant cornea and conjunctiva

endocrine/exocrine glands

abnormal Meibomian gland acinus morphology ( J:175263 )

• at P21, mutant Meibomian glands exhibit disorganized, variably sized acini

abnormal Meibomian gland development ( J:175263 )

• a Meibomian gland bud is noted at P6 suggesting timely induction, but appears disorganized; this feature becomes more prominent at P11 and P21

• at P21, the swollen eyelids are hypercellular and contain severely malformed Meibomian glands with disorganized acini

enlarged sebaceous gland ( J:175263 )

• at P21, mutant sebaceous glands are significantly enlarged

abnormal lacrimal gland morphology ( J:175263 )

• at 8 weeks of age, mutant lacrimal glands display excessive vasculature and disrupted acinar organization, unlike wild-type controls

lacrimal gland necrosis ( J:175263 )

• at 8 weeks of age, mutant lacrimal glands display interspersed dark spots resembling necrotic spots

abnormal Meibomian gland physiology ( J:175263 )

• at P21, an uneven lipid accumulation is noted in the Meibomian gland ducts

lacrimal gland inflammation ( J:175263 )

• at 8 weeks of age, mutant lacrimal glands display numerous infiltrating cells, indicating inflammation

immune system

lacrimal gland inflammation ( J:175263 )

• at 8 weeks of age, mutant lacrimal glands display numerous infiltrating cells, indicating inflammation

integument

abnormal Meibomian gland acinus morphology ( J:175263 )

• at P21, mutant Meibomian glands exhibit disorganized, variably sized acini

abnormal Meibomian gland development ( J:175263 )

• a Meibomian gland bud is noted at P6 suggesting timely induction, but appears disorganized; this feature becomes more prominent at P11 and P21

• at P21, the swollen eyelids are hypercellular and contain severely malformed Meibomian glands with disorganized acini

enlarged sebaceous gland ( J:175263 )

• at P21, mutant sebaceous glands are significantly enlarged

abnormal Meibomian gland physiology ( J:175263 )

• at P21, an uneven lipid accumulation is noted in the Meibomian gland ducts

enlarged hair follicles ( J:175263 )

• at P21, mutant eyelids contain significantly enlarged hair follicles

growth/size/body

eyelid edema ( J:175263 )

• mutant eyelids are swollen at P6, P11, P21 and at 10 weeks of age

muscle

abnormal extraocular muscle morphology ( J:175263 )

• at 8 weeks of age, a thicker extra-ocular muscle is observed

homeostasis/metabolism

eyelid edema ( J:175263 )

• mutant eyelids are swollen at P6, P11, P21 and at 10 weeks of age

craniofacial

eyelid edema ( J:175263 )

• mutant eyelids are swollen at P6, P11, P21 and at 10 weeks of age