Phenotypes associated with this allele

• Allele Symbol: Ilk^tm1Star
• Allele Name: targeted mutation 1, Rene St-Arnaud
• Allele ID: MGI:2668459
• Summary: 8 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Ilk^tm1Star/Ilk^tm1Star	involves: 129S1/Sv * 129X1/SvJ	MGI:5009419
cn2	Ilk^tm1Star/Ilk^tm2Star Tg(Acp5-cre)1Star/0	involves: 129S1/Sv * 129X1/SvJ * C57BL/6	MGI:5502225
cn3	Ilk^tm1Star/Ilk^tm1Star Tg(Col2a1-cre)1Star/?	involves: 129S1/Sv * 129X1/SvJ * C57BL/6	MGI:2671930
cn4	Ilk^tm1Star/Ilk^tm1Star Tg(KRT14-cre)1Amc/0	involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * CBA	MGI:5009418
cn5	Ilk^tm1Star/Ilk^tm1Star Tg(Krt1-15-cre/PGR*)22Cot/0	involves: 129S1/Sv * 129X1/SvJ * C57BL/6J * SJL/J	MGI:5009341
cn6	Gt(ROSA)26Sor^tm1(EYFP)Cos/Gt(ROSA)26Sor^+ Ilk^tm1Star/Ilk^tm1Star Tg(Krt1-15-cre/PGR*)22Cot/0	involves: 129S1/Sv * 129X1/SvJ * C57BL/6J * SJL/J	MGI:5009342
cn7	Ilk^tm1Star/Ilk^tm1Star Tg(NPHS2-cre)295Lbh/0	involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * SJL	MGI:5432357
cn8	Ilk^tm1Star/Ilk^tm1Star Tg(Ckmm-cre)1Lrsn/0	involves: 129S1/Sv * 129X1/SvJ * FVB/N	MGI:5907206

Genotype
MGI:5009419

hm1

• Allelic Composition: Ilk^tm1Star/Ilk^tm1Star
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ

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

integument

decreased keratinocyte migration ( J:172934 )

• in culture, keratinocytes treated with a cre-expressing adenovirus exhibit reduced spreading, altered migration, and impaired directional migration compared with wild-type mice

• however, keratinocyte spreading and forward movement is rescued by Rac1 G12V and RhoG

abnormal keratinocyte morphology ( J:172934 )

• in culture, keratinocytes are round and phase-contrast bright unlike control cells

cellular

decreased keratinocyte migration ( J:172934 )

• in culture, keratinocytes treated with a cre-expressing adenovirus exhibit reduced spreading, altered migration, and impaired directional migration compared with wild-type mice

• however, keratinocyte spreading and forward movement is rescued by Rac1 G12V and RhoG

Genotype
MGI:5502225

cn2

• Allelic Composition: Ilk^tm1Star/Ilk^tm2Star; Tg(Acp5-cre)1Star/0
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6

growth/size/body

growth/size/body region phenotype ( J:197593 )

N • mice are phenotypically normal and show no differences in size or weight relative to controls at birth or throughout their lifespan

craniofacial

craniofacial phenotype ( J:197593 )

N • animals have normal tooth eruption

skeleton

increased osteoclast cell number ( J:197593 )

• numbers of osteoclasts in the primary spongiosa are significantly increased at 6 weeks

abnormal osteoclast physiology ( J:197593 )

• in vitro differentiated osteoclasts plate on dentin slices display decreased bone resorpion activity (45% lower osteoclastic resorption activity); osteoclasts show impaired resorption in vivo also

increased bone volume ( J:197593 )

• tibial bone volume is increased by 24% compared to controls at 6 weeks

increased trabecular bone thickness ( J:197593 )

• trabecular thickness of tibiae at 6 weeks is increased by 44% compared to controls

hematopoietic system

increased osteoclast cell number ( J:197593 )

• numbers of osteoclasts in the primary spongiosa are significantly increased at 6 weeks

abnormal osteoclast physiology ( J:197593 )

• in vitro differentiated osteoclasts plate on dentin slices display decreased bone resorpion activity (45% lower osteoclastic resorption activity); osteoclasts show impaired resorption in vivo also

immune system

increased osteoclast cell number ( J:197593 )

• numbers of osteoclasts in the primary spongiosa are significantly increased at 6 weeks

abnormal osteoclast physiology ( J:197593 )

• in vitro differentiated osteoclasts plate on dentin slices display decreased bone resorpion activity (45% lower osteoclastic resorption activity); osteoclasts show impaired resorption in vivo also

Genotype
MGI:2671930

cn3

• Allelic Composition: Ilk^tm1Star/Ilk^tm1Star; Tg(Col2a1-cre)1Star/?
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6

growth/size/body

disproportionate dwarf ( J:84273 )

• newborn homozygotes were smaller than normal with the small size becoming more conspicuous with age

• forelimbs and hind limbs were shortened but not deformed

skeleton

abnormal skeleton development ( J:84273 )

chondrodystrophy ( J:84273 )

• moderate chondrodysplasia

• growth plate most affected in the proliferating zone

• Cyclin D1 expression reduced in the proliferating zone

• poor columnar organization

• chondrocytes more rounded

• chondrocyte differentiation unaffected

• apoptosis normal

Genotype
MGI:5009418

cn4

• Allelic Composition: Ilk^tm1Star/Ilk^tm1Star; Tg(KRT14-cre)1Amc/0
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * CBA

mortality/aging

postnatal lethality, complete penetrance ( J:172934 )

• median survival is 4 days

integument

decreased keratinocyte proliferation ( J:172934 )

• in culture

skin edema ( J:172934 )

skin inflammation ( J:172934 )

abnormal hair growth ( J:172934 )

• by P3

abnormal hair follicle development ( J:172934 )

• hair follicles exhibit severe growth retardation compared to in control mice

• no follicles are apparent beyond stage 4 unlike in control mice

decreased hair follicle number ( J:172934 )

• at P4

abnormal hair follicle physiology ( J:172934 )

• hair follicles exhibit decreased cell proliferation compared to in control mice

abnormal epidermal layer morphology ( J:172934 )

• mice exhibit increased intracellular epidermal spaces compared with control mice

acanthosis ( J:172934 )

blistering ( J:172934 )

• mice exhibit microblisters at the junction of the basal layer and the basement membrane on different parts of the body, including dorsal skin, the footpads, and along the forelimbs and hindlimbs, unlike in control mice

• blisters are more common in areas of high friction

scaly skin ( J:172934 )

abnormal skin pigmentation ( J:172934 )

• reduced as early as P1

thin skin ( J:172934 )

decreased skin tensile strength ( J:172934 )

• fragile skin

homeostasis/metabolism

skin edema ( J:172934 )

growth/size/body

postnatal growth retardation ( J:172934 )

• as early as P1

immune system

skin inflammation ( J:172934 )

pigmentation

abnormal skin pigmentation ( J:172934 )

• reduced as early as P1

cellular

decreased keratinocyte proliferation ( J:172934 )

• in culture

Genotype
MGI:5009341

cn5

• Allelic Composition: Ilk^tm1Star/Ilk^tm1Star; Tg(Krt1-15-cre/PGR*)22Cot/0
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6J * SJL/J

homeostasis/metabolism

delayed wound healing ( J:172933 )

• in RU486-treated mice

Genotype
MGI:5009342

cn6

• Allelic Composition: Gt(ROSA)26Sor^tm1(EYFP)Cos/Gt(ROSA)26Sor⁺; Ilk^tm1Star/Ilk^tm1Star; Tg(Krt1-15-cre/PGR*)22Cot/0
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6J * SJL/J

homeostasis/metabolism

abnormal wound healing ( J:172933 )

• during wound regeneration, RU486-treated mice exhibit YFP+ cells in the suprabasal layers but not the basal layers unlike in control mice

delayed wound healing ( J:172933 )

• in RU486-treated mice

integument

abnormal hair follicle development ( J:172933 )

• following treatment with RU486, plated YFP+ hair follicle stem cells do not exhibit spreading unlike YFP- cells

Genotype
MGI:5432357

cn7

• Allelic Composition: Ilk^tm1Star/Ilk^tm1Star; Tg(NPHS2-cre)295Lbh/0
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * SJL

mortality/aging

decreased survivor rate ( J:129286 )

• only a few mice survive beyond 6 months of age

premature death ( J:129244 , J:129286 )

• mice exhibit a reduced life span with a median age of death at 19 weeks, and 100% mortality by 32 weeks of age (J:129244)

• mice begin to die at 10 weeks of age; most die of renal failure at ~3-4 months of age (J:129286)

growth/size/body

decreased body weight ( J:129286 )

• significantly decreased body weight first noted at 10 weeks of age

renal/urinary system

detached podocyte ( J:129244 , J:129286 )

• focal detachment from the basement membrane at 8-12 weeks of age (J:129244)

• by 10 weeks of age, podocytes are sometimes detached from the GBM and found in the lumens of dilated tubules (J:129286)

• however, no podocyte detachment is observed at 4 weeks of age (J:129286)

increased kidney apoptosis ( J:129286 )

• marked apoptosis in the tubulointerstitial area of the kidney at 10 weeks of age, unlike in control mice

increased podocyte apoptosis ( J:129286 )

• a significant number of TUNEL+ podocytes is noted in the lumens of tubules at 10 weeks of age, suggesting that detached podocytes undergo apoptotic death

• however, no podocyte detachment or apoptosis is observed at 4 weeks of age, when albuminuria is pronounced

increased urine protein level ( J:129244 , J:129286 )

• selective albuminuria first detected at 2 weeks that progresses rapidly to unselective proteinuria by 4-12 weeks of age (J:129244)

• massive proteinuria at 12 weeks of age (J:129244)

• significantly increased urine total protein at 4 and 10 weeks of age (J:129286)

albuminuria ( J:129244 , J:129286 )

• selective albuminuria first seen at 2 weeks of age (J:129244)

• albuminuria precedes the development of focal segmental glomerulosclerosis lesions (J:129244)

• dramatically increased urine albumin levels are first noted at 4 weeks of age, progressing to severe albuminuria at 10 weeks of age (J:129286)

tubulointerstitial nephritis ( J:129244 , J:129286 )

• tubulointerstitial changes with mononuclear infiltration at 12 weeks of age (J:129244)

• advanced tubulointerstitial inflammation in end-stage kidneys (J:129244)

• mild, patchy mononuclear inflammatory infiltrate in the interstitium at 10 weeks of age (J:129286)

abnormal kidney morphology ( J:129244 )

• at 16 weeks of age, nephrotic end-stage kidneys appear yellow and display a rough surface

abnormal podocyte morphology ( J:129244 , J:129286 )

• occasional prominent single podocytes, predominantly in juxtamedullary glomeruli at 2-3 weeks of age (J:129244)

• prominent podocytes in juxtamedullary glomeruli with pseudocysts and vacuolization, focal microvillous transformation, and multifocal foot process effacement at 4 weeks of age (J:129244)

• advanced vacuolization, microvillous transformation, widespread foot process effacement, and focal detachment from the basement membrane at 8-12 weeks of age (J:129244)

• at 4 weeks of age, an aberrant distribution of nephrin and alpha-actinin-4 is observed, unlike in control podocytes; however, the localization of podocin and synaptopodin remains intact (J:129286)

fused podocyte foot processes ( J:129286 )

• fused foot processes are noted at 10 weeks of age

podocyte foot process effacement ( J:129244 , J:129286 )

• multifocal foot process effacement at 4 weeks of age (J:129244)

• widespread foot process effacement at 8-12 weeks of age (J:129244)

• slight podocyte foot process effacement with a narrower slit diaphragm is occasionally seen at 2 weeks of age, prior to the onset of albuminuria (J:129286)

• marked foot process effacement is noted at 4 weeks of age, and becomes severe by 10 weeks of age (J:129286)

abnormal podocyte slit diaphragm morphology ( J:129244 , J:129286 )

• loss of slit diaphragm noted with progression to unselective proteinuria (J:129244)

• at 4 weeks of age, foot processes are adhered to GBM as continuous cytoplasmic processes, leading to the disappearance of the slit diaphragm (J:129286)

• a narrower slit diaphragm is occasionally found in some podocyte areas at 2 weeks of age (J:129286)

decreased podocyte number ( J:129286 )

• a ~70% reduction in the number of podocytes per glomerulus is first seen at 10 weeks of age

podocyte microvillus transformation ( J:129244 , J:129286 )

• focal microvillous transformation at 4 weeks of age (J:129244)

• at 4 weeks of age, massive microvilli are formed on the surface of podocytes, unlike in control podocytes (J:129286)

abnormal renal glomerulus basement membrane morphology ( J:129244 , J:129286 )

• no alterations in key GBM components (fibronectin, laminins, and collagen IV isoforms) are observed; however, alpha3-integrins are relocalized into a granular pattern along the GBM, consistent with altered integrin-mediated matrix assembly, at 3 weeks of age (J:129244)

• at 10 weeks of age, podocyte foot processes are sometimes detached from the GBM, leading to a naked GBM on the side of the Bowman space (J:129286)

• an irregular GBM shape is also observed in some areas of the glomeruli at 4 weeks of age (J:129286)

increased renal glomerulus basement membrane thickness ( J:129244 , J:129286 )

• homogeneous thickening of the GBM at 3 weeks of age (J:129244)

• true harmonic mean GBM thickness is increased by 22.6% at 3 weeks of age (J:129244)

• diffuse and irregular thickening of the GBM with electron-lucent areas at 8-12 weeks of age (J:129244)

• increased GBM thickness is observed in some areas of the glomeruli at 4 weeks of age (J:129286)

abnormal renal glomerulus morphology ( J:129286 )

• primary glomerular lesions first seen at 10 weeks of age

abnormal glomerular capillary morphology ( J:129244 )

• distorted capillaries at 4 and 12 weeks of age

expanded mesangial matrix ( J:129244 , J:129286 )

• occasional segmental mesangial expansion with increased matrix deposition at 4 weeks of age (J:129244)

• advanced mesangial expansion with increased matrix deposition at 12 weeks of age (J:129244)

• moderate to marked mesangial expansion at 10 weeks of age (J:129286)

glomerulosclerosis ( J:129244 , J:129286 )

• mice develop progressive focal segmental glomerulosclerosis (J:129244)

• advanced focal and segmental sclerotic lesions associated with tubulointerstitial changes at 8-16 weeks of age (J:129244)

• diffuse glomerulosclerosis in end-stage kidneys (J:129244)

• segmental glomerulosclerosis to global sclerosis at 10 weeks of age (J:129286)

glomerular crescent ( J:129244 )

• crescent formation at 12 weeks of age

renal glomerular synechia ( J:129244 )

• tuft adhesions to Bowman's capsule at 12 weeks of age

renal glomerulus hypertrophy ( J:129286 )

• enlarged glomerular size at 10 weeks of age

renal interstitial fibrosis ( J:129244 , J:129286 )

• at 12 and 16 weeks of age (J:129244)

• mild interstitial fibrosis at 10 weeks of age (J:129286)

renal tubule atrophy ( J:129244 )

• at 12 weeks of age

dilated renal tubule ( J:129286 )

• extensive tubular dilation distended by proteinaceous fluid and cellular debris at 10 weeks of age

abnormal glomerular filtration barrier function ( J:129244 )

• progressive filtration barrier failure

kidney failure ( J:129244 , J:129286 )

• mice die of kidney failure (J:129244)

• age-dependent deterioration of kidney function (J:129286)

homeostasis/metabolism

increased circulating creatinine level ( J:129286 )

• significantly increased serum creatinine levels at 10 but not at 4 weeks of age

increased blood urea nitrogen level ( J:129244 )

• at 12 weeks of age

increased circulating cholesterol level ( J:129244 )

• at 12 weeks of age

increased urine protein level ( J:129244 , J:129286 )

• selective albuminuria first detected at 2 weeks that progresses rapidly to unselective proteinuria by 4-12 weeks of age (J:129244)

• massive proteinuria at 12 weeks of age (J:129244)

• significantly increased urine total protein at 4 and 10 weeks of age (J:129286)

albuminuria ( J:129244 , J:129286 )

• selective albuminuria first seen at 2 weeks of age (J:129244)

• albuminuria precedes the development of focal segmental glomerulosclerosis lesions (J:129244)

• dramatically increased urine albumin levels are first noted at 4 weeks of age, progressing to severe albuminuria at 10 weeks of age (J:129286)

immune system

tubulointerstitial nephritis ( J:129244 , J:129286 )

• tubulointerstitial changes with mononuclear infiltration at 12 weeks of age (J:129244)

• advanced tubulointerstitial inflammation in end-stage kidneys (J:129244)

• mild, patchy mononuclear inflammatory infiltrate in the interstitium at 10 weeks of age (J:129286)

cardiovascular system

abnormal glomerular capillary morphology ( J:129244 )

• distorted capillaries at 4 and 12 weeks of age

cellular

detached podocyte ( J:129244 , J:129286 )

• focal detachment from the basement membrane at 8-12 weeks of age (J:129244)

• by 10 weeks of age, podocytes are sometimes detached from the GBM and found in the lumens of dilated tubules (J:129286)

• however, no podocyte detachment is observed at 4 weeks of age (J:129286)

increased kidney apoptosis ( J:129286 )

• marked apoptosis in the tubulointerstitial area of the kidney at 10 weeks of age, unlike in control mice

increased podocyte apoptosis ( J:129286 )

• a significant number of TUNEL+ podocytes is noted in the lumens of tubules at 10 weeks of age, suggesting that detached podocytes undergo apoptotic death

• however, no podocyte detachment or apoptosis is observed at 4 weeks of age, when albuminuria is pronounced

Genotype
MGI:5907206

cn8

• Allelic Composition: Ilk^tm1Star/Ilk^tm1Star; Tg(Ckmm-cre)1Lrsn/0
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * FVB/N

mortality/aging

premature death ( J:112174 )

• all mice die suddenly starting at about 6 weeks of age, between 6 and 12 weeks of age and with a median age of death of 2 months

• mice often die during mating and during attempted surgical procedures and hearts show evidence of stress at the molecular level, indicating increased cardiac physiological stress

cardiovascular system

abnormal heart morphology ( J:112174 )

• disaggregation of adjacent cardiomyocytes within heart tissue

• however, mice show no evidence of skeletal muscle defects

enlarged heart ( J:112174 )

• hearts are grossly enlarged, with a 2-fold increase in the heart-to-body mass ratio

dilated heart left ventricle ( J:112174 )

• dilated left ventricular chambers

cardiac interstitial fibrosis ( J:112174 )

• fibrosis in left ventricle and accumulation of interstitial fibrotic tissue in hearts

dilated cardiomyopathy ( J:112174 )

• mice exhibit enlarged hearts and impaired contraction of hearts leading to heart failure by 6-12 weeks of age

decreased cardiac muscle contractility ( J:112174 )

♂ • ejection fraction is greatly reduced, indicating impaired pumping capacity of the heart

abnormal heart echocardiography feature ( J:112174 )

♂ • echocardiography indicates an increase in end diastolic and end systolic areas and reduced ejection fraction

congestive heart failure ( J:112174 )

• mice exhibit labored breathing, lack of physical strength, disorientation, problems with balance, and hunched, withdrawn behavior before death, indicating heart failure

muscle

dilated cardiomyopathy ( J:112174 )

• mice exhibit enlarged hearts and impaired contraction of hearts leading to heart failure by 6-12 weeks of age

decreased cardiac muscle contractility ( J:112174 )

♂ • ejection fraction is greatly reduced, indicating impaired pumping capacity of the heart

growth/size/body

enlarged heart ( J:112174 )

• hearts are grossly enlarged, with a 2-fold increase in the heart-to-body mass ratio

cellular

cardiac interstitial fibrosis ( J:112174 )

• fibrosis in left ventricle and accumulation of interstitial fibrotic tissue in hearts

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
dilated cardiomyopathy		DOID:12930	OMIM:PS115200	J:112174