Phenotypes associated with this allele

• Allele Symbol: Dicer1^tm1Smr
• Allele Name: targeted mutation 1, Sarah E Millar
• Allele ID: MGI:3641051
• Summary: 4 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cn1	Dicer1^tm1Smr/Dicer1^tm1Smr Pax8^tm1.1(cre)Mbu/Pax8^+	involves: 129P2/OlaHsd * 129S7/SvEvBrd	MGI:5792829
cn2	Dicer1^tm1Smr/Dicer1^tm1Smr Tg(KRT5-rtTA)1Glk/0 Tg(tetO-cre)1Jaw/0	involves: 129S7/SvEvBrd * C57BL/6 * FVB/N	MGI:5431583
cn3	Dicer1^tm1Smr/Dicer1^tm1Smr Tg(KRT14-cre)52Smr/0	involves: 129S7/SvEvBrd * C57BL/6J * SJL/J	MGI:3641079
cn4	Dicer1^tm1Smr/Dicer1^tm1Smr Tg(Myh6-cre)2182Mds/0	involves: 129S7/SvEvBrd * FVB/N	MGI:5906349

Genotype
MGI:5792829

cn1

• Allelic Composition: Dicer1^tm1Smr/Dicer1^tm1Smr; Pax8^{tm1.1(cre)Mbu}/Pax8⁺
• Genetic Background: involves: 129P2/OlaHsd * 129S7/SvEvBrd

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

renal/urinary system

increased kidney apoptosis ( J:229188 )

• apoptosis is frequently seen in shedding cells in both the Bowman space and in the lumen of the tubules, occurring more frequently at P50

increased kidney cell proliferation ( J:229188 )

• the tubular epithelium and parietal cells of the renal corpuscles show increased cellular proliferation in the phase of cyst growth

decreased urine osmolality ( J:229188 )

• at P30, urinary osmolality is lower, with no changes in urinary ouput or in collecting duct distribution

increased urine protein level ( J:229188 )

• mice develop progressively massive proteinuria, consisting mainly of albuminuria that is already higher at P30

albuminuria ( J:229188 )

• seen by P30

abnormal kidney morphology ( J:229188 )

• kidneys at P50 have a rough surface

abnormal renal tubule epithelial cell primary cilium morphology ( J:229188 )

• at P50, primary cilia are rare in the epithelium of dilating tubules and absent in enlarged cysts with flattened epithelium, indicating a progressive loss of primary cilia with cyst enlargement

kidney cortex cyst ( J:229188 )

• at P50, mice exhibit cortical cysts

• cysts originate from the renal corpuscles of the cortex and are absent in the outer and inner medulla

decreased kidney collecting duct number ( J:229188 )

• the density of collecting ducts is lower at P50

abnormal renal corpuscle morphology ( J:229188 )

• the tubular epithelium and parietal cells of the renal corpuscles show increased cellular proliferation in the phase of cyst growth, before flattening of the cystic epithelium

dilated renal glomerular capsule ( J:229188 )

• dilatation of the parietal cells of the Bowman capsule

abnormal renal glomerulus morphology ( J:229188 )

• glomeruli progressively shrink

• mice develop glomerulocystic disease

renal interstitial fibrosis ( J:229188 )

• epithelium lining the cyst flattens and interstitial fibrosis develops

decreased kidney weight ( J:229188 )

• mice present lower kidney weight at P50, with the ratio of kidney weight/body weight being lower at P50 but not P30

dilated renal tubule ( J:229188 )

• tubular dilatations are mainly cortical and develop progressively at P50

pale kidney ( J:229188 )

• kidneys at P50 have a paler color

decreased renal glomerular filtration rate ( J:229188 )

isosthenuria ( J:229188 )

• progressive impairment of urinary concentrating ability

polyuria ( J:229188 )

• increase in urine output at P50 but not P30

cellular

abnormal renal tubule epithelial cell primary cilium morphology ( J:229188 )

• at P50, primary cilia are rare in the epithelium of dilating tubules and absent in enlarged cysts with flattened epithelium, indicating a progressive loss of primary cilia with cyst enlargement

increased kidney apoptosis ( J:229188 )

• apoptosis is frequently seen in shedding cells in both the Bowman space and in the lumen of the tubules, occurring more frequently at P50

increased kidney cell proliferation ( J:229188 )

• the tubular epithelium and parietal cells of the renal corpuscles show increased cellular proliferation in the phase of cyst growth

growth/size/body

decreased body weight ( J:229188 )

• mice present lower body weight at P30

kidney cortex cyst ( J:229188 )

• at P50, mice exhibit cortical cysts

• cysts originate from the renal corpuscles of the cortex and are absent in the outer and inner medulla

homeostasis/metabolism

decreased urine osmolality ( J:229188 )

• at P30, urinary osmolality is lower, with no changes in urinary ouput or in collecting duct distribution

increased urine protein level ( J:229188 )

• mice develop progressively massive proteinuria, consisting mainly of albuminuria that is already higher at P30

albuminuria ( J:229188 )

• seen by P30

behavior/neurological

increased fluid intake ( J:229188 )

• increase in water intake at P30 and P50

Genotype
MGI:5431583

cn2

• Allelic Composition: Dicer1^tm1Smr/Dicer1^tm1Smr; Tg(KRT5-rtTA)1Glk/0; Tg(tetO-cre)1Jaw/0
• Genetic Background: involves: 129S7/SvEvBrd * C57BL/6 * FVB/N

integument

integument phenotype ( J:183487 )

N • doxycycline-treated mice retain hair follicle stem cells in early telogen and anagen

abnormal coat/ hair morphology ( J:183487 )

• hair phenotype in doxycycline-treated mice appears more rapidly than in Drosha^tm1Litt/Drosha^tm1Litt Tg(KRT5-rtTA)1Glk Tg(tetO-cre)1Jaw mice

abnormal hair growth ( J:183487 )

• failure of hair regrowth in doxycycline-treated mice

• failure of regression at P20 in doxycycline-treated mice and remained in an abnormal growth phase

• following hair plucking, doxycycline-treated mice fail to sustain hair growth unlike control mice

alopecia ( J:183487 )

• after P14 in doxycycline-treated mice

waved hair ( J:183487 )

• external hair becomes wavy between P12 and P14 in doxycycline-treated mice

abnormal hair shaft morphology ( J:183487 )

• in doxycycline-treated mice likely due to matrix cell apoptosis

abnormal hair follicle morphology ( J:183487 )

• at P17 in doxycycline-treated mice after degradation begins

abnormal hair follicle inner root sheath morphology ( J:183487 )

• fewer differentiation cell in doxycycline-treated mice following plucking-induced anagen initiation

abnormal hair follicle bulge morphology ( J:183487 )

• at P59 doxycycline-treated mice exhibit loss of bulge stem cells unlike in control mice

• however, bulge stem cells are present at P20 and P22

hair follicle degeneration ( J:183487 )

• with extrusion of abnormally keratinized cellular material in doxycycline-treated mice

small hair follicles ( J:183487 )

• in doxycycline-treated mice following plucking-induced anagen initiation

abnormal hair cycle catagen phase ( J:183487 )

• failure of catagen in doxycycline-treated mice

abnormal hair follicle regression ( J:183487 )

• failure of regression at P20 in doxycycline-treated mice

epidermal hyperplasia ( J:183487 )

• by P20, doxycycline-treated mice exhibit thickened interfollicular epidermis compared with control mice

dry skin ( J:183487 )

• mice treated with doxycycline exhibit a temporary phenotype of dry scaly skin that is resolved in an anterior-posterior direction

scaly skin ( J:183487 )

• mice treated with doxycycline exhibit a temporary phenotype of dry scaly skin that is resolved in an anterior-posterior direction

abnormal skin physiology ( J:183487 )

cellular

increased apoptosis ( J:183487 )

• doxycycline-treated mice exhibit matrix cell apoptosis with DNA damage response unlike in control mice

growth/size/body

decreased body size ( J:183487 )

• in doxycycline-treated mice

Genotype
MGI:3641079

cn3

• Allelic Composition: Dicer1^tm1Smr/Dicer1^tm1Smr; Tg(KRT14-cre)52Smr/0
• Genetic Background: involves: 129S7/SvEvBrd * C57BL/6J * SJL/J

mortality/aging

premature death ( J:110268 )

• less affected mice survive up to 2.5 months

postnatal lethality, incomplete penetrance ( J:110268 )

• severely affected mutants die within a few days of birth

growth/size/body

postnatal growth retardation ( J:110268 )

• newborn mice appear normal but by P7 are stunted with respect to growth compared to wild-type lettermates

integument

delayed hair appearance ( J:110268 )

• at P7 mice lack external hair growth

abnormal hair shaft morphology ( J:110268 )

• hair shaft structures are underdeveloped, and hair shafts do not extend beyond the level of the epidermis

small hair follicle bulb ( J:110268 )

• the hair bulbs are smaller than those in controls

abnormal hair follicle development ( J:110268 )

• in newborn skin, follicle growth is stunted

• secondary hair follicles fail to extend into the dermis

abnormal hair follicle orientation ( J:110268 )

• when viewed from the dermal aspect, hair follicles are misangled and fail to display the normal anterior-posterior polarity seen in control skin

• by P7, mutant hair follicles are misangled and wavy

hair follicle degeneration ( J:110268 )

• by P49 hair follicles have degenerated in large stretches of mutant skin and have been replaced by cyst structures or clumps of disorganized epithelial cells

decreased hair follicle cell proliferation ( J:110268 )

• hair follicle proliferation is reduced in newborns

abnormal epidermal layer morphology ( J:110268 )

• the skin of mutants displays evaginating dermal cells which are engulfed by epidermal cells

• at P7 epidermal proliferation is increased compared with controls

• the epidermis is expanded compared to controls at P7 and is that way at P49

thick epidermis ( J:110268 )

• at P49 and P63, mutant epidermis is thickened with increased numbers of basal and suprabasal layers

Genotype
MGI:5906349

cn4

• Allelic Composition: Dicer1^tm1Smr/Dicer1^tm1Smr; Tg(Myh6-cre)2182Mds/0
• Genetic Background: involves: 129S7/SvEvBrd * FVB/N

Dilated cardiomyopathy in Dicer1^tm1Smr/Dicer1^tm1Smr Tg(Myh6-cre)2182Mds/0 hearts

growth/size/body

enlarged heart ( J:131962 )

mortality/aging

postnatal lethality, complete penetrance ( J:131962 )

• all mice die within 4 days after birth

behavior/neurological

decreased locomotor activity ( J:131962 )

• pups become fragile and exhibit decreased spontaneous activity preceding death

cardiovascular system

abnormal myocardial fiber morphology ( J:131962 )

• integrity of cardiomyocytes is impaired

disorganized myocardium ( J:131962 )

fetal cardiomyocyte disarray ( J:131962 )

• neonatal cardiomyocytes show disarrayed myofibrils

enlarged heart ( J:131962 )

dilated heart left ventricle ( J:131962 )

dilated cardiomyopathy ( J:131962 )

decreased heart ventricle muscle contractility ( J:131962 )

• decrease in fractional shortening and an increase in the left ventricle posterior wall thickness at end diastole without change at end systole, indicating a loss of ventricle force generation

• hearts exhibit dysregulation of cardiac contractile protein expression

• however, sarcoplasmic reticulum calcium uptake rates are normal in hearts

abnormal heart echocardiography feature ( J:131962 )

• echocardiography indicates severe left ventricle dilation with a decrease in fractional shortening and an increase in the left ventricle posterior wall thickness at end diastole without change at end systole, indicating a loss of ventricle force generation

decreased heart rate ( J:131962 )

• hearts only beat about half of the rate

congestive heart failure ( J:131962 )

cellular

increased cardiomyocyte apoptosis ( J:131962 )

• increase in apoptosis in the left atrium of P2 hearts and in restricted areas of the ventricular apex and left ventricle wall, however no increase in apoptosis is seen before P0

• however, cardiomyocyte proliferation, cell size, and cell number are normal

homeostasis/metabolism

abnormal atrial thrombosis ( J:131962 )

• accumulation of blood clots and/or thrombin in the left atrium

abnormal ventricular thrombosis ( J:131962 )

• accumulation of blood clots and/or thrombin in the left ventricle

muscle

abnormal myocardial fiber morphology ( J:131962 )

• integrity of cardiomyocytes is impaired

disorganized myocardium ( J:131962 )

dilated cardiomyopathy ( J:131962 )

decreased heart ventricle muscle contractility ( J:131962 )

• decrease in fractional shortening and an increase in the left ventricle posterior wall thickness at end diastole without change at end systole, indicating a loss of ventricle force generation

• hearts exhibit dysregulation of cardiac contractile protein expression

• however, sarcoplasmic reticulum calcium uptake rates are normal in hearts

increased cardiomyocyte apoptosis ( J:131962 )

• increase in apoptosis in the left atrium of P2 hearts and in restricted areas of the ventricular apex and left ventricle wall, however no increase in apoptosis is seen before P0

• however, cardiomyocyte proliferation, cell size, and cell number are normal

abnormal sarcomere morphology ( J:131962 )

• less sarcomeres in heart ventricles and the sarcomeres that are present are disarrayed and shorter

• however, intercalated discs appear normal

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
dilated cardiomyopathy		DOID:12930	OMIM:PS115200	J:131962