Phenotypes associated with this allele

• Allele Symbol: Lamc1^tm1Umr
• Allele Name: targeted mutation 1, Ulrike Mayer
• Allele ID: MGI:2183782
• Summary: 3 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Lamc1^tm1Umr/Lamc1^tm1Umr	either: (involves: 129S1/Sv * 129X1/SvJ) or (involves: 129S1/Sv * 129X1/SvJ * C57BL/6)	MGI:3761185
hm2	Lamc1^tm1Umr/Lamc1^tm1Umr	involves: 129S1/Sv * 129X1/SvJ	MGI:3761289
hm3	Lamc1^tm1Umr/Lamc1^tm1Umr	involves: 129S1/Sv * 129X1/SvJ * C57BL/6	MGI:3761157

Genotype
MGI:3761185

hm1

• Allelic Composition: Lamc1^tm1Umr/Lamc1^tm1Umr
• Genetic Background: either: (involves: 129S1/Sv * 129X1/SvJ) or (involves: 129S1/Sv * 129X1/SvJ * C57BL/6)

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

mortality/aging

neonatal lethality, complete penetrance ( J:76368 )

• remaining mice die soon after birth

embryonic lethality during organogenesis, incomplete penetrance ( J:76368 )

• 40% of mice die prior to E11.5 of unknown causes

reproductive system

abnormal reproductive system morphology ( J:76368 )

• ovaries and testies are present and morphologically normal

absent seminal vesicle ( J:76368 )

♂ • seminal vesicles are absent

absent uterus ( J:76368 )

♀

abnormal epididymis morphology ( J:76368 )

♂ • the normal architecture of the epididymis is lost

absent vas deferens ( J:76368 )

♂

embryo

abnormal Mullerian duct morphology ( J:76368 )

• at E13.5, the Mullerian duct is blind-ending

abnormal Wolffian duct morphology ( J:76368 )

• in 18 embryos lacking metanephric kidney induction, the Wolffian duct is blind-ending

• at E10.5, the basement membranes of the elongating Wolffian duct is discontinuous whereas it is continuous in wild-type mice

renal/urinary system

kidney microaneurysm ( J:76368 )

• frequently the Bowmann's capsule is partially or completely filled with red blood cells

kidney cyst ( J:76368 )

• only male mice exhibit cystic enlargements

abnormal renal glomerular capsule morphology ( J:76368 )

• frequently the Bowmann's capsule is partially or completely filled with red blood cells

abnormal renal glomerulus morphology ( J:76368 )

• mice that possess kidneys exhibit 30% less mature glomeruli than wild-type mice; of these 60% develop normally while the rest show either a reduced (25%) or missing (15%) capillary tuft

decreased renal glomerulus number ( J:76368 )

• mice that possess kidneys exhibit 30% less mature glomeruli than wild-type mice

abnormal kidney development ( J:76368 )

• at E13.5, mice possess fewer tubuli than wild-type mice

absent metanephros ( J:76368 )

• at E13.5, the metanephroi are absent

• however, the metanephric blastema is present

hydronephrosis ( J:76368 )

• three male mice with kidneys exhibit hydronephric kidneys with a thinned parenchyma and the ureter connects aberrantly to the vas deferens or in one case the epididymys

absent kidney ( J:76368 )

• at E18.5, 80% of mice lack both kidneys

• however, adrenal glands are present and morphologically normal

single kidney ( J:76368 )

• at E18.5, 10% of mice lack one kidney

abnormal ureter morphology ( J:76368 )

• three male mice with kidneys exhibit hydronephric kidneys with a thinned parenchyma and the ureter connects aberrantly to the vas deferens or in one case the epididymis

absent ureteric bud ( J:76368 )

• at E11, in most embryos the ureteric buds are absent

kidney failure ( J:76368 )

• at E18.8, kidneys that are present in 10% of mice are non-functional

respiratory system

abnormal lung saccule morphology ( J:76368 )

• at E18.5, prealveolar sacculi are immature and only poorly inflated

• at E18.5, only 10% of prealveolar sacculi form

• however, at E11.5 and E13.5 lung development is normal and by E18.5 surfactant protein C is detected

thick lung-associated mesenchyme ( J:76368 )

• at E18.5, mesenchymal thickening between the terminal airspaces is observed

small lung ( J:76368 )

• at E18.5, lung size is smaller and more compact than in wild-type mice

abnormal bronchus morphology ( J:76368 )

• at E18.5, the major bronchial trees are more compact and smaller than in wild-type mice

• however, at E13.5 and E15.5 lung development is normal and by E18.5 surfactant protein C is detected

growth/size/body

kidney cyst ( J:76368 )

• only male mice exhibit cystic enlargements

decreased fetal size ( J:76368 )

• at E18.5, mice are 20% smaller than wild-type mice

endocrine/exocrine glands

absent seminal vesicle ( J:76368 )

♂ • seminal vesicles are absent

cardiovascular system

kidney microaneurysm ( J:76368 )

• frequently the Bowmann's capsule is partially or completely filled with red blood cells

cellular

abnormal basement membrane morphology ( J:76368 )

• only 30% of mice exhibit normal basement membranes, in 30% only amorphously deposited material is detected, and in the remaining mice the basement membrane is completely missing and epithelial cell protrusions enter into the empty space

• at E10.5, the basement membranes of the elongating Wolffian duct is discontinuous whereas it is continuous in wild-type mice

Genotype
MGI:3761289

hm2

• Allelic Composition: Lamc1^tm1Umr/Lamc1^tm1Umr
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ

nervous system

intracranial hemorrhage ( J:124247 )

• between E16 and E18, mice exhibit hemorrhages in the brain

abnormal neuron differentiation ( J:124247 )

• between E10 and E13, neurons form ectopically when the pial basement membrane is disrupted

• however, neuron proliferation and migration are normal

abnormal radial glial cell morphology ( J:119018 , J:124247 )

• the continuous band of FABP7 staining of the radial glial endfeet is absent in the cortex (J:119018)

• however, radial glial organization in the intermediate and ventricular zone, proliferation, neurogenesis, and interkinetic nuclear migration are normal (J:119018)

• at E14, radial glial endfeet are missing in the cerebral cortex (J:119018)

• radial glial cell endfeets often end short of the pial surface by 50 um and their terminal branches are disorganized (J:124247)

• between E10 and E13, retracted endfeet are restricted to areas where the pial basement membrane is disrupted but in older mice with intact pial basement membranes the endfeet remain retracted (J:124247)

abnormal neural tube closure ( J:124247 )

• 5% of mice exhibit exencephaly due to a defect in neural closure at E9

abnormal Cajal-Retzius cell morphology ( J:124247 )

• at E16, Cajal-Retzius cells either are distributed in random areas of the cortices, are widely distributed throughout the upper half of the cortex, are entirely missing or are ectopically located outside of the meninges

• in areas where Cajal-Retzius cells are missing the cortical plate neurons aggregate as ectopias within the marginal zone and the meninges and in areas where then Cajal-Retzius cells have ended their migration prematurely the cortical plate neurons are displaced into a deeper layer

• however, the 50 um distance between the cortical plate neurons and the Cajal-Retzius cells is maintained

• in segments missing meningeal cells the Cajal-Retzius cells are missing

abnormal cortical plate morphology ( J:119018 )

• unlike in wild-type mice, ectopic FABP7+ and IFAPRC2+ cells are detected in the cortical plate

decreased brain size ( J:124247 )

• brain and cerebral cortices are smaller than in wild-type mice

abnormal cerebral cortex morphology ( J:119018 , J:124247 )

• unlike in wild-type mice that contain virtually no dividing cells (0.6%) in their cortex, these cells constitute 4.6% of all precursors in the cortex of homozygous mice (J:119018)

• at E18, some pyramidal cells in the cortex are replaced by GABAnergic interneurons (J:119018)

• at E18, the cerebral cortex is thinner laterally but longer compared to in wild-type mice (J:119018)

• neuronal migration and cortex architecture are severely disrupted (J:119018)

• however, no increase in cell death is detected in the cortex at E18 (J:119018)

• brain and cerebral cortices are smaller than in wild-type mice (J:124247)

• between E16 and E18, mice exhibit hemorrhages in the brain and numerous bumps are observed on the pial surface of the brain giving the cortical hemispheres a mulberry-like appearance (J:124247)

• while marginal and intermediate zones are present, dysplasias in the cortical plate and marginal zone are observed (J:124247)

• however, dysplasias were variable and did not correlate with hemorrhages (J:124247)

• unlike in wild-type mice, the basement membrane is discontinuous and is associated with an irregular meningeal layer (J:124247)

• in areas where Cajal-Retzius cells are missing the cortical plate neurons aggregate as ectopias within the marginal zone and the meninges and in areas where then Cajal-Retzius cells have ended their migration prematurely the cortical plate neurons are displaced into a deeper layer (J:124247)

• however, the 50 um distance between the cortical plate neurons and the Cajal-Retzius cells is maintained (J:124247)

thin cerebral cortex ( J:119018 )

• at E18, the lateral cortex is reduced by 11% compared to in wild-type mice

• the medial cortex is normal

abnormal meninges morphology ( J:124247 )

• unlike in wild-type mice, the meningeal layer is irregular

• in segments missing meningeal cells the Cajal-Retzius cells are missing

exencephaly ( J:124247 )

• 5% of mice exhibit exencephaly due to a defect in neural closure at E9

vision/eye

abnormal retina morphology ( J:124247 )

• while the basement membrane in the retina is continuous it is ruptured in many locations and cells penetrate from the retina into the vitrenous body

• neuroepithelial endfeet are more widely separated than in wild-type mice and the basement membrane covering the gaps is thin and fragile

growth/size/body

decreased body size ( J:124247 )

• mice are smaller in size than wild-type mice

cardiovascular system

intracranial hemorrhage ( J:124247 )

• between E16 and E18, mice exhibit hemorrhages in the brain

embryo

abnormal neural tube closure ( J:124247 )

• 5% of mice exhibit exencephaly due to a defect in neural closure at E9

cellular

abnormal neuron differentiation ( J:124247 )

• between E10 and E13, neurons form ectopically when the pial basement membrane is disrupted

• however, neuron proliferation and migration are normal

abnormal radial glial cell morphology ( J:119018 , J:124247 )

• the continuous band of FABP7 staining of the radial glial endfeet is absent in the cortex (J:119018)

• however, radial glial organization in the intermediate and ventricular zone, proliferation, neurogenesis, and interkinetic nuclear migration are normal (J:119018)

• at E14, radial glial endfeet are missing in the cerebral cortex (J:119018)

• radial glial cell endfeets often end short of the pial surface by 50 um and their terminal branches are disorganized (J:124247)

• between E10 and E13, retracted endfeet are restricted to areas where the pial basement membrane is disrupted but in older mice with intact pial basement membranes the endfeet remain retracted (J:124247)

abnormal basement membrane morphology ( J:119018 , J:124247 )

• mice exhibit a widespread disruption of the basement membrane along the blood vessels in the cortex (J:119018)

• unlike in wild-type mice, the basement membrane is discontinuous and is associated with an irregular meningeal layer (J:124247)

• while the retinal basement membrane is continuous it is ruptured in many locations and cells penetrate from the retina into the vitreous body (J:124247)

• the basement membrane covering the gaps between neuroepithelial cells in the retina is thin and fragile (J:124247)

• the vascular basement membrane in the eye is discontinuous and parts of the endothelial cells protrude through the gaps (J:124247)

• the pial basement membrane is thin and irregular compared to in wild-type mice (J:124247)

• between E10 and E13, 30% of the pial basement membrane is disrupted in all mice and neurons form ectopically when the pial basement membrane is disrupted (J:124247)

• however, the basement membrane of the diencephalon is normal and continuous (J:124247)

• gaps in the basement membrane of the spinal cord lead to motorneurons migrating into the adjacent mesenchyme (J:124247)

Genotype
MGI:3761157

hm3

• Allelic Composition: Lamc1^tm1Umr/Lamc1^tm1Umr
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6

nervous system

abnormal brain development ( J:126065 )

• proliferation of marginal zone neural progenitors of the cerebral cortex is increased compared to in wild-type mice and proliferating cells do not contain Pax6 or Tbr2