Phenotypes associated with this allele

• Allele Symbol: Lama5^tm1Jhm
• Allele Name: targeted mutation 1, Jeffrey H Miner
• Allele ID: MGI:1934917
• Summary: 5 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Lama5^tm1Jhm/Lama5^tm1Jhm	involves: 129 * C57BL/6J	MGI:2176867
ht2	Lama5^tm1Jhm/Lama5^+	involves: 129S1/Sv * 129X1/SvJ	MGI:3625355
cn3	Lama5^tm1Jhm/Lama5^tm2Jhm Tg(SFTPC-rtTA)5Jaw/? Tg(tetO-cre)1Jaw/?	involves: 129S1/Sv * 129X1/SvJ	MGI:3613082
cn4	Lama5^tm2Jhm/Lama5^tm1Jhm Tg(NPHS2-cre)295Lbh/0	involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * CBA * SJL	MGI:5432560
cx5	Lama5^tm1Jhm/Lama5^tm1Jhm Tg(ACTB-Lama5/LAMA1)1Jhm/0	involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * CBA	MGI:3822743

Genotype
MGI:2176867

hm1

• Allelic Composition: Lama5^tm1Jhm/Lama5^tm1Jhm
• Genetic Background: involves: 129 * C57BL/6J

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

Syndactyly in Lama5^tm1Jhm/Lama5^tm1Jhm embryos

mortality/aging

lethality throughout fetal growth and development, complete penetrance ( J:51557 )

• no homozygotes live beyond E17

• defects apparent after E9

limbs/digits/tail

abnormal limb morphology ( J:51557 )

• distal limbs change from "paddle-like" shape to "club-like"

syndactyly ( J:51557 )

• digits fail to separate

• pattern forms normally

• syndactyly more severe in forelimbs, some separation of digits 1 and 5 in the hind limb by E14.5

craniofacial

absent neurocranium ( J:51557 )

• failure of the cranial vault to form

embryo

incomplete rostral neuropore closure ( J:51557 )

• anterior neural tube fails to close

abnormal placenta morphology ( J:51557 )

abnormal placental labyrinth vasculature morphology ( J:51557 )

• complexity of fetal blood vessels is reduced and diameter of vessels is increased

decreased placental labyrinth size ( J:51557 )

• small in size

abnormal trophoblast layer morphology ( J:51557 )

• trophoblast and fetal endothelial layers often separated by cell free space with the basal lamina associating with the endothelial layer

nervous system

incomplete rostral neuropore closure ( J:51557 )

• anterior neural tube fails to close

exencephaly ( J:51557 )

renal/urinary system

abnormal glomerular capillary morphology ( J:59925 )

• lack of vascularized glomerulus

abnormal glomerular capillary endothelium morphology ( J:59925 )

• extruded endothelial cells

abnormal mesangial cell morphology ( J:59925 )

• extruded mesangial cells

abnormal podocyte morphology ( J:59925 )

• avascular clusters of podocytes

abnormal kidney development ( J:59925 )

• attenuated nephrogenesis

• one or both kidneys fail to develop by E13.5-E16.5 in 20% of mutants

small kidney ( J:59925 )

• kidneys were smaller than normal in mutant mice with kidneys

absent kidney ( J:59925 )

• one or both kidneys fail to develop by E13.5-E16.5 in 20% of mutants

absent ureter ( J:59925 )

• ureter sometimes absent as well

impaired branching involved in ureteric bud morphogenesis ( J:84903 )

• attenuated ureteric branching

respiratory system

small lung ( J:77264 )

• at E12.5 and E16.5, mutant lungs are smaller than normal

abnormal right lung morphology ( J:77264 )

• lobar separation of the right lung is incomplete to varying degrees

• incomplete lobar septation is evident as early as E12.5

• at E16.5, there is no evidence of septation of the cranial lobe, the medial lobe or the accessory lobe

abnormal visceral pleura morphology ( J:77264 )

• visceral pleura lacks basement membrane

digestive/alimentary system

abnormal intestine morphology ( J:84903 )

• proportionately short intestine but of normal diameter

• excessive folding of intestinal loops, sometimes with fusing of muscular layer and absence of mesentery or serosal layer

abnormal intestinal goblet cell morphology ( J:84903 )

• fewer in number

abnormal intestinal epithelium morphology ( J:84903 )

• villi formed but fewer in number

growth/size/body

megacephaly ( J:51557 )

• enlarged and misshapened head in 60% of embryos

decreased fetal size ( J:51557 )

• smaller than normal at E14

skeleton

absent neurocranium ( J:51557 )

• failure of the cranial vault to form

cardiovascular system

abnormal glomerular capillary morphology ( J:59925 )

• lack of vascularized glomerulus

abnormal glomerular capillary endothelium morphology ( J:59925 )

• extruded endothelial cells

abnormal placental labyrinth vasculature morphology ( J:51557 )

• complexity of fetal blood vessels is reduced and diameter of vessels is increased

cellular

abnormal intestinal goblet cell morphology ( J:84903 )

• fewer in number

abnormal mesangial cell morphology ( J:59925 )

• extruded mesangial cells

impaired basement membrane formation ( J:77264 )

• E16.5, no typical basement membrane is assembled in the visceral pleura

• scattered deposits of electron-dense material that may contain components of basement membrane are rarely observed

Genotype
MGI:3625355

ht2

• Allelic Composition: Lama5^tm1Jhm/Lama5⁺
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ

craniofacial

abnormal tooth development ( J:108325 )

• at E13.5, mutant mice fail to form a distinct single layer of dental epithelium unlike heterozygous controls

• at E14.5, mutant mice do not form an enamel knot structure and the size of the tooth germ is reduced compared to controls; the number of proliferating cells in the outer and inner epithelia and surrounding mesenchyme is reduced by 50% in mutant mice

• at E17.5, the inner dental epithelium is not polarized, forms an elongated shape and remains rounded in shape, in contrast to morphology in controls

growth/size/body

abnormal tooth development ( J:108325 )

• at E13.5, mutant mice fail to form a distinct single layer of dental epithelium unlike heterozygous controls

• at E14.5, mutant mice do not form an enamel knot structure and the size of the tooth germ is reduced compared to controls; the number of proliferating cells in the outer and inner epithelia and surrounding mesenchyme is reduced by 50% in mutant mice

• at E17.5, the inner dental epithelium is not polarized, forms an elongated shape and remains rounded in shape, in contrast to morphology in controls

skeleton

abnormal tooth development ( J:108325 )

• at E13.5, mutant mice fail to form a distinct single layer of dental epithelium unlike heterozygous controls

• at E14.5, mutant mice do not form an enamel knot structure and the size of the tooth germ is reduced compared to controls; the number of proliferating cells in the outer and inner epithelia and surrounding mesenchyme is reduced by 50% in mutant mice

• at E17.5, the inner dental epithelium is not polarized, forms an elongated shape and remains rounded in shape, in contrast to morphology in controls

Genotype
MGI:3613082

cn3

• Allelic Composition: Lama5^tm1Jhm/Lama5^tm2Jhm; Tg(SFTPC-rtTA)5Jaw/?; Tg(tetO-cre)1Jaw/?
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ

mortality/aging

neonatal lethality, complete penetrance ( J:104565 )

• animals exposed to doxycycline from E6.5 die within a few hours of birth from respiratory failure

respiratory system

abnormal lung vasculature morphology ( J:104565 )

• severely reduced density of lung capillary network in newborn animals exposed to doxycycline from E6.5, associated with reduced VEGF expression in mutant lungs

abnormal lung development ( J:104565 )

• areas of thin lung mesenchyme and upregulation of integrin alpha 3 (Lama5 receptor) in newborn animals exposed to doxycycline from E6.5

thin lung-associated mesenchyme ( J:104565 )

• areas of thin lung mesenchyme in newborn animals exposed to doxycycline from E6.5

pulmonary hypoplasia ( J:104565 )

• total lung parenchyma is reduced

abnormal pulmonary alveolus morphology ( J:104565 )

• airspaces of newborn animals exposed to doxycycline from E6.5 are filled with amorphous proteinaceous material and cellular debris not seen in controls

abnormal pulmonary alveolus epithelium morphology ( J:104565 )

• delayed or impaired differentiation of distal alveolar epithelium in newborn animals exposed to doxycycline from E6.5

• mutant peripheral airspaces are often lined with cuboidal epithelium

absent type I pneumocytes ( J:104565 )

• virtual absence of alveolar type I cells in newborn animals exposed to doxycycline from E6.5

decreased type II pneumocyte number ( J:104565 )

• significant reduction of alveolar type II cells in newborn animals exposed to doxycycline from E6.5

overexpanded pulmonary alveolus ( J:104565 )

• enlarged distal airspaces in newborn animals exposed to doxycycline from E6.5

respiratory distress ( J:104565 )

• newborn animals exposed to doxycycline from E6.5 display labored breathing

respiratory failure ( J:104565 )

homeostasis/metabolism

cyanosis ( J:104565 )

• newborn animals exposed to doxycycline from E6.5 display cyanosis

cardiovascular system

abnormal lung vasculature morphology ( J:104565 )

• severely reduced density of lung capillary network in newborn animals exposed to doxycycline from E6.5, associated with reduced VEGF expression in mutant lungs

cellular

increased apoptosis ( J:104565 )

• in lungs of newborn animals exposed to doxycycline starting at E6.5

decreased cell proliferation ( J:104565 )

• in lungs of newborn animals exposed to doxycycline from E6.5

Genotype
MGI:5432560

cn4

• Allelic Composition: Lama5^tm2Jhm/Lama5^tm1Jhm; Tg(NPHS2-cre)295Lbh/0
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * CBA * SJL

renal/urinary system

increased urine protein level ( J:185850 )

• animals show mild proteinuria early in life (3 weeks), and progress to the nephrotic range of disease

hematuria ( J:185850 )

• observed with age

tubulointerstitial nephritis ( J:185850 )

abnormal kidney morphology ( J:185850 )

• yellowing of the kidneys is observed with age

podocyte foot process effacement ( J:185850 )

abnormal renal glomerulus basement membrane morphology ( J:185850 )

• increased thickness, a moth-eated appearance and irregular contours with frequent subepithelial outpocketings are observed at late disease stages

increased renal glomerulus basement membrane thickness ( J:185850 )

expanded mesangial matrix ( J:185850 )

• observed at late stages of disease

glomerulosclerosis ( J:185850 )

• observed at late stages of disease

homeostasis/metabolism

increased circulating cholesterol level ( J:185850 )

• observed with age

decreased circulating serum albumin level ( J:185850 )

• observed with age

edema ( J:185850 )

• mice become edematous with age

increased urine protein level ( J:185850 )

• animals show mild proteinuria early in life (3 weeks), and progress to the nephrotic range of disease

hematuria ( J:185850 )

• observed with age

immune system

tubulointerstitial nephritis ( J:185850 )

Genotype
MGI:3822743

cx5

• Allelic Composition: Lama5^tm1Jhm/Lama5^tm1Jhm; Tg(ACTB-Lama5/LAMA1)1Jhm/0
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * CBA

mortality/aging

premature death ( J:142595 )

• unlike Lama5^tm1Jhm homozygotes, mice several month before dieing from kidney disease

nervous system

abnormal neuromuscular synapse morphology ( J:142595 )

• maturation of postsynaptic neuromuscular junctions (NMJs) is delayed compared to in wild-type mice

• however, maturation of presynaptic NMJs is normal

renal/urinary system

abnormal renal/urinary system physiology ( J:142595 )

• mice die from kidney disease