Phenotypes associated with this allele

• Allele Symbol: Lamb2^tm1Jrs
• Allele Name: targeted mutation 1, Joshua R Sanes
• Allele ID: MGI:2138070
• Summary: 5 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Lamb2^tm1Jrs/Lamb2^tm1Jrs	involves: 129S1/Sv * 129X1/SvJ	MGI:2175097
hm2	Lamb2^tm1Jrs/Lamb2^tm1Jrs	involves: 129S1/Sv * 129X1/SvJ * C57BL/6J	MGI:4941483
cn3	Fgfr2^tm1Dor/Fgfr2^tm1Dor Lamb2^tm1Jrs/Lamb2^tm1Jrs Tg(Mnx1-cre)1Jrs/?	involves: 129S1/Sv * 129X1/SvJ * C57BL/6	MGI:3766403
cx4	Lamb2^tm1Jrs/Lamb2^tm1Jrs Lamc3^tm1.1Wjbr/Lamc3^tm1.1Wjbr	B6.129-Lamc3^tm1.1Wjbr Lamb2^tm1Jrs	MGI:4941482
cx5	Lamb2^tm1Jrs/Lamb2^tm1Jrs Tg(Ckm-Lamb2)1Jhm/0 Tg(Nphs1-Lamb2*S83R)#Jhm/0	involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * CBA	MGI:6378619

Genotype
MGI:2175097

hm1

• Allelic Composition: Lamb2^tm1Jrs/Lamb2^tm1Jrs
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ

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

mortality/aging

postnatal lethality, complete penetrance ( J:23783 )

• between P15 and P30

growth/size/body

postnatal growth retardation ( J:23783 , J:27732 )

• after 1 week of age (J:23783)

• grow at a normal rate for 6 days after birth, then cease growing by P8 and do not gain weight from P8 to P14 (J:27732)

nervous system

abnormal retina photoreceptor morphology ( J:77308 )

• reduction in retina thickness is attributable almost entirely to a decrease in photoreceptor length

short photoreceptor inner segment ( J:77308 )

• inner segments fail to increase in length at 3-4 weeks after birth are about 50% shorter at P25

short photoreceptor outer segment ( J:77308 )

• outer segments fail to increase in length at 3-4 weeks after birth are about 50% shorter at P25, however they still express rhodopsin

abnormal retina rod cell morphology ( J:77308 )

• abnormal rod photoreceptor synapses

abnormal neuromuscular synapse morphology ( J:23783 )

failure of neuromuscular synapse postsynaptic differentiation ( J:23783 )

• unbranched end plate and absence of junctional folds at neuromuscular synapse

failure of neuromuscular synapse presynaptic differentiation ( J:23783 )

• abnormal Schwann cell processes, absence of active zones and abnormal distribution of synaptic vesicles at neuromuscular synapses

abnormal miniature endplate potential ( J:23783 )

• altered miniature endplate potential frequency

renal/urinary system

increased urine protein level ( J:23783 , J:27732 )

• urinary protein increased approximately 100-fold between P2 and P15 (J:23783)

• develop massive proteinuria due to failure of the glomerular filtration barrier (J:27732)

albuminuria ( J:27732 )

• albumin is the major protein component of the proteinuria

glomerulonephritis ( J:23783 )

fused podocyte foot processes ( J:23783 )

• the foot processes of visceral epithelial cells are frequently fused

abnormal renal glomerulus basement membrane morphology ( J:27732 )

• glomeruli form in normal numbers and kidneys appear normal, however the renal glomerular basement membrane occasionally shows thickening and outpocketing

• the glomerular basement membrane remains rich in Lamb1, indicating a compensatory response for lack of Lamb2

increased renal glomerulus basement membrane thickness ( J:27732 )

• occasional thickening

abnormal glomerular filtration barrier function ( J:27732 )

• failure of the glomerular filtration barrier

homeostasis/metabolism

increased urine protein level ( J:23783 , J:27732 )

• urinary protein increased approximately 100-fold between P2 and P15 (J:23783)

• develop massive proteinuria due to failure of the glomerular filtration barrier (J:27732)

albuminuria ( J:27732 )

• albumin is the major protein component of the proteinuria

immune system

glomerulonephritis ( J:23783 )

behavior/neurological

lethargy ( J:77308 )

• mutants are lethargic and move about with difficulty

vision/eye

increased retina apoptosis ( J:77308 )

• exhibit about twice the amount of programmed cell death at P15, however still exhibit the basic developmental trend of a decrease in dying cells with age

abnormal retina morphology ( J:77308 )

• outer retina contains aberrant processes in the interphotoreceptor matrix

abnormal retina photoreceptor morphology ( J:77308 )

• reduction in retina thickness is attributable almost entirely to a decrease in photoreceptor length

short photoreceptor inner segment ( J:77308 )

• inner segments fail to increase in length at 3-4 weeks after birth are about 50% shorter at P25

short photoreceptor outer segment ( J:77308 )

• outer segments fail to increase in length at 3-4 weeks after birth are about 50% shorter at P25, however they still express rhodopsin

abnormal retina rod cell morphology ( J:77308 )

• abnormal rod photoreceptor synapses

abnormal retina outer plexiform layer morphology ( J:77308 )

• the outer plexiform layer is disrupted as only 7% of observed rod invaginating synapses appear normal, whereas the inner plexiform layer is undisturbed

• the outer plexiform layers rarely contain fully formed triads and instead exhibit a variety of malformations

• tirads and dyads (relatively mature synapses) account for only about 55% of the ribbon synapses

• most conspicuous malformation is floating ribbons, fully assembled ribbon complexes with associated synaptic vesicles that are unapposed to any postsynaptic element

decreased total retina thickness ( J:77308 )

• reduction in thickness of the retina is first noticeable at P13

abnormal eye electrophysiology ( J:77308 )

• abnormal electroretinograms; amplitude of the b-wave and slope of the b-wave intensity-response function are both decreased

• the b-wave is flatter and approaches a linear function, rather than the exponential shape of the control, indicating that photoreceptor to bipolar transmission is not as effective

cellular

increased retina apoptosis ( J:77308 )

• exhibit about twice the amount of programmed cell death at P15, however still exhibit the basic developmental trend of a decrease in dying cells with age

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
nephrosis		DOID:2527		J:27732
Pierson syndrome		DOID:0060852	OMIM:609049	J:106005

Genotype
MGI:4941483

hm2

• Allelic Composition: Lamb2^tm1Jrs/Lamb2^tm1Jrs
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6J

vision/eye

abnormal retina morphology ( J:169656 )

• at P20 the basement membrane show local disruptions in its structure

abnormal Muller cell morphology ( J:169656 )

• at the sites of breaks in the basement membrane, Muller cell basal terminals form a disorganized array from the inner plexiform layer through the ganglion cell layer

• at other points, Muller cell terminals form aggregates at blood vessels

abnormal amacrine cell morphology ( J:169656 )

• at P20, the perikarya of type I tyrosine hydroxylase expressing (TH) neurons are slightly larger compared to wild-type controls

• however, no abnormalities are detected in cholinergic or AII amacrine cells

decreased amacrine cell number ( J:169656 )

• decrease in the density of type I TH neurons at P20

abnormal retina development ( J:169656 )

• about a 1 day delay in the increase in density of type I TH neurons is detected between P3 and P5

abnormal retina inner limiting membrane morphology ( J:169656 )

• at the sites of breaks in the basement membrane, Muller cell basal terminals form a disorganized array from the inner plexiform layer through the ganglion cell layer

abnormal eye physiology ( J:169656 )

• the tyrosine hydroxylase immunoreactivity of type II amacrine cells is increased at P20

nervous system

abnormal Muller cell morphology ( J:169656 )

• at the sites of breaks in the basement membrane, Muller cell basal terminals form a disorganized array from the inner plexiform layer through the ganglion cell layer

• at other points, Muller cell terminals form aggregates at blood vessels

abnormal amacrine cell morphology ( J:169656 )

• at P20, the perikarya of type I tyrosine hydroxylase expressing (TH) neurons are slightly larger compared to wild-type controls

• however, no abnormalities are detected in cholinergic or AII amacrine cells

decreased amacrine cell number ( J:169656 )

• decrease in the density of type I TH neurons at P20

Genotype
MGI:3766403

cn3

• Allelic Composition: Fgfr2^tm1Dor/Fgfr2^tm1Dor; Lamb2^tm1Jrs/Lamb2^tm1Jrs; Tg(Mnx1-cre)1Jrs/?
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6

nervous system

abnormal synaptic vesicle clustering ( J:126496 )

• at P14, vesicles were highly clustered at synaptic site, but were abundant in preterminal portions

Genotype
MGI:4941482

cx4

• Allelic Composition: Lamb2^tm1Jrs/Lamb2^tm1Jrs; Lamc3^tm1.1Wjbr/Lamc3^tm1.1Wjbr
• Genetic Background: B6.129-Lamc3^tm1.1Wjbr Lamb2^tm1Jrs

vision/eye

abnormal retina morphology ( J:169656 )

• at P20 the basement membrane shows local disruptions in its structure

abnormal Muller cell morphology ( J:169656 )

• at the sites of breaks in the basement membrane, Muller cell basal terminals form a disorganized array from the inner plexiform layer (IPL) through the ganglion cell layer

• at other points, Muller cell terminals form aggregates at blood vessels

• the overall length is reduced and the fine lateral branches within the IPL are disarrayed

• at P12, the vertical shafts are thinner in the regions of basement membrane breaks

abnormal amacrine cell morphology ( J:169656 )

• at P20, the perikarya of type I tyrosine hydroxylase expressing (TH) neurons are somewhat smaller compared to wild-type controls and both single null mice

• however, no abnormalities are detected in cholinergic or AII amacrine cells

decreased amacrine cell number ( J:169656 )

• decrease in the density of type I TH neurons at P20

abnormal retina development ( J:169656 )

• the delay in the increase in density of type I TH neurons detected between P3 and P5 is increased compared to mice homozygous null for Lamb2 alone

abnormal eye physiology ( J:169656 )

• the tyrosine hydroxylase immunoreactivity of type II amacrine cells is increased at P20

nervous system

abnormal Muller cell morphology ( J:169656 )

• at the sites of breaks in the basement membrane, Muller cell basal terminals form a disorganized array from the inner plexiform layer (IPL) through the ganglion cell layer

• at other points, Muller cell terminals form aggregates at blood vessels

• the overall length is reduced and the fine lateral branches within the IPL are disarrayed

• at P12, the vertical shafts are thinner in the regions of basement membrane breaks

abnormal amacrine cell morphology ( J:169656 )

• at P20, the perikarya of type I tyrosine hydroxylase expressing (TH) neurons are somewhat smaller compared to wild-type controls and both single null mice

• however, no abnormalities are detected in cholinergic or AII amacrine cells

decreased amacrine cell number ( J:169656 )

• decrease in the density of type I TH neurons at P20

Genotype
MGI:6378619

cx5

• Allelic Composition: Lamb2^tm1Jrs/Lamb2^tm1Jrs; Tg(Ckm-Lamb2)1Jhm/0; Tg(Nphs1-Lamb2*S83R)#Jhm/0
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * CBA

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:280129 )

N • mice do not become proteinuric, even when aged to over 1 year

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
NOT	Pierson syndrome	DOID:0060852	OMIM:609049	J:280129