Phenotypes associated with this allele

• Allele Symbol: Pdpk1^tm1.1Mlw
• Allele Name: targeted mutation 1.1, Margaret A Lawlor
• Allele ID: MGI:2677461
• Summary: 4 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Pdpk1^tm1.1Mlw/Pdpk1^tm1.1Mlw	involves: BALB/c	MGI:2677592
cn2	Pdpk1^tm1.1Mlw/Pdpk1^tm1.1Mlw Rag2^tm1Fwa/Rag2^tm1Fwa Tnfrsf4^tm2(cre)Nik/Tnfrsf4^+ Gt(ROSA)26Sor^tm1(EYFP)Cos/Gt(ROSA)26Sor^+	involves: 129S/SvEv * 129X1/SvJ * C57BL/6	MGI:5697630
cn3	Pdpk1^tm1.1Mlw/Pdpk1^tm1.1Mlw Tnfrsf4^tm2(cre)Nik/Tnfrsf4^+ Gt(ROSA)26Sor^tm1(EYFP)Cos/Gt(ROSA)26Sor^+	involves: 129X1/SvJ * C57BL/6	MGI:5697628
cn4	Pdpk1^tm1.1Mlw/Pdpk1^tm1.1Mlw Tg(Ckmm-cre)5Khn/?	involves: BALB/c	MGI:2677593

Genotype
MGI:2677592

hm1

• Allelic Composition: Pdpk1^tm1.1Mlw/Pdpk1^tm1.1Mlw
• Genetic Background: involves: BALB/c

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

normal phenotype

no abnormal phenotype detected ( J:85894 )

• homozygotes born at expected ratio

• normal size

Genotype
MGI:5697630

cn2

• Allelic Composition: Pdpk1^tm1.1Mlw/Pdpk1^tm1.1Mlw; Rag2^tm1Fwa/Rag2^tm1Fwa; Tnfrsf4^tm2(cre)Nik/Tnfrsf4⁺; Gt(ROSA)26Sor^tm1(EYFP)Cos/Gt(ROSA)26Sor⁺
• Genetic Background: involves: 129S/SvEv * 129X1/SvJ * C57BL/6

mortality/aging

premature death ( J:226194 )

• mice succumb to disease at 12-16 weeks of age

integument

abnormal keratinocyte differentiation ( J:226194 )

• marker analysis indicates impaired keratinocyte differentiation

dermatitis ( J:226194 )

• mice develop mild skin dermatitis

epidermal hyperplasia ( J:226194 )

immune system

dermatitis ( J:226194 )

• mice develop mild skin dermatitis

cellular

abnormal keratinocyte differentiation ( J:226194 )

• marker analysis indicates impaired keratinocyte differentiation

Genotype
MGI:5697628

cn3

• Allelic Composition: Pdpk1^tm1.1Mlw/Pdpk1^tm1.1Mlw; Tnfrsf4^tm2(cre)Nik/Tnfrsf4⁺; Gt(ROSA)26Sor^tm1(EYFP)Cos/Gt(ROSA)26Sor⁺
• Genetic Background: involves: 129X1/SvJ * C57BL/6

mortality/aging

premature death ( J:226194 )

• mice develop a wasting syndrome and succumb to disease by 11 weeks of age

growth/size/body

cachexia ( J:226194 )

enlarged spleen ( J:226194 )

• mice develop an enlarged spleen

integument

abnormal hypodermis fat layer morphology ( J:226194 )

• loss of hypodermal fat

abnormal keratinocyte differentiation ( J:226194 )

• marker analysis indicates impaired keratinocyte differentiation

impaired skin barrier function ( J:226194 )

• mice with advanced disease show loss of skin barrier integrity at 7-8 weeks of age

dermatitis ( J:226194 )

• mice develop severe, systemic dermatitis starting at 5 weeks of age

• inflammation is not seen in the lung, liver, kidney or gut

premature hair loss ( J:226194 )

• dermatitis is accompanied by hair loss

hair follicle degeneration ( J:226194 )

• loss of hair follicles

hyperkeratosis ( J:226194 )

epidermal hyperplasia ( J:226194 )

• mild epidermal hyperplasia and microabsceess are seen at 3 weeks of age but not at 10 days of age

scaly skin ( J:226194 )

• skin contains epidermal scales

skin lesions ( J:226194 )

• skin of mice with advanced disease contains lesions with epidermal damage, resulting in loss of skin barrier integrity

skin hyperplasia ( J:226194 )

thick skin ( J:226194 )

• dermatitis is accompanied by skin thickening

skin fibrosis ( J:226194 )

• increase in dermal fibrosis

immune system

enlarged spleen ( J:226194 )

• mice develop an enlarged spleen

abnormal regulatory T cell number ( J:226194 )

• decrease in the frequency of Foxp3+ CD25+ Tregs with a corresponding increase in Foxp3-CD25+ effector T cells

abnormal T cell physiology ( J:226194 )

• CD4 T cells exhibit an activated phenotype

• mice develop systemic T helper type 2 immunity

enlarged lymph nodes ( J:226194 )

• mice develop peripheral lymphadenopathy

dermatitis ( J:226194 )

• mice develop severe, systemic dermatitis starting at 5 weeks of age

• inflammation is not seen in the lung, liver, kidney or gut

homeostasis/metabolism

impaired skin barrier function ( J:226194 )

• mice with advanced disease show loss of skin barrier integrity at 7-8 weeks of age

hematopoietic system

enlarged spleen ( J:226194 )

• mice develop an enlarged spleen

abnormal regulatory T cell number ( J:226194 )

• decrease in the frequency of Foxp3+ CD25+ Tregs with a corresponding increase in Foxp3-CD25+ effector T cells

abnormal T cell physiology ( J:226194 )

• CD4 T cells exhibit an activated phenotype

• mice develop systemic T helper type 2 immunity

cellular

abnormal keratinocyte differentiation ( J:226194 )

• marker analysis indicates impaired keratinocyte differentiation

adipose tissue

abnormal hypodermis fat layer morphology ( J:226194 )

• loss of hypodermal fat

Genotype
MGI:2677593

cn4

• Allelic Composition: Pdpk1^tm1.1Mlw/Pdpk1^tm1.1Mlw; Tg(Ckmm-cre)5Khn/?
• Genetic Background: involves: BALB/c

mortality/aging

premature death ( J:85498 )

• normal numbers born

• normal phenotype and survive to wk 5

• growth normal

• breathe and eat normally

• normal activity

• not diabetic to wk 8

• all die at age 5-11 wks

• drop in activity 2-3 days before death and weight loss

• noncardiac muscle normal

cardiovascular system

abnormal cardiovascular system morphology ( J:85498 )

abnormal heart morphology ( J:85498 )

• by 6 wks, collagen levels, ANF and beta-myosin heavy chain levels are increased in hearts

• increased sensitivity of cardiomyocytes to hypoxia

abnormal myocardial fiber morphology ( J:85498 )

• cardiomyocytes appear more separated from each other

• reduction in cardiomyocyte volume

increased heart atrium size ( J:85498 )

• atria enlarge by 6 wks and massively inflated at death

small heart ( J:85498 )

• from 2-4 weeks, hearts became progressively smaller in relative terms but otherwise were normal

• by 6 weeks hearts were much smaller with reduced muscle mass due to smaller cardiomyocytes

myocardium hypoplasia ( J:85498 )

• muscle mass of hearts is significantly reduced

abnormal heart ventricle morphology ( J:85498 )

abnormal heart right ventricle morphology ( J:85498 )

• right ventricle is significantly enlarged by 6 weeks of age

heart right ventricle hypertrophy ( J:85498 )

• by 6 weeks

thin ventricular wall ( J:85498 )

• by 6 weeks

• extremely thin by death

dilated cardiomyopathy ( J:85498 )

• by 8 weeks of age, exhibit an increase in Z-line thickness, a feature of dilated cardiomyopathy

abnormal cardiovascular system physiology ( J:85498 )

• echocardiograms at 5-6 weeks revealing development of heart failure

decreased cardiac muscle contractility ( J:85498 )

• reduced fractional shortening and ejection fraction

growth/size/body

heart right ventricle hypertrophy ( J:85498 )

• by 6 weeks

decreased body weight ( J:85498 )

• observe a significant reduction in body weight 2-3 days before mutants die

muscle

abnormal myocardial fiber morphology ( J:85498 )

• cardiomyocytes appear more separated from each other

• reduction in cardiomyocyte volume

myocardium hypoplasia ( J:85498 )

• muscle mass of hearts is significantly reduced

heart right ventricle hypertrophy ( J:85498 )

• by 6 weeks

dilated cardiomyopathy ( J:85498 )

• by 8 weeks of age, exhibit an increase in Z-line thickness, a feature of dilated cardiomyopathy

decreased cardiac muscle contractility ( J:85498 )

• reduced fractional shortening and ejection fraction

abnormal Z line morphology ( J:85498 )

• thicker Z-line by 8 weeks of age