Phenotypes associated with this allele

• Allele Symbol: L1cam^tm1Sor
• Allele Name: targeted mutation 1, Philippe Soriano
• Allele ID: MGI:1857443
• Summary: 5 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cx1	L1cam^tm1Sor/L1cam^+ Nrcam^tm1Gmt/Nrcam^tm1Gmt	involves: 129S6/SvEvTac * 129S7/SvEvBrd * Swiss Webster	MGI:3806025
cx2	L1cam^tm1Sor/Y Nrcam^tm1Gmt/Nrcam^+	involves: 129S6/SvEvTac * 129S7/SvEvBrd * Swiss Webster	MGI:3806030
cx3	L1cam^tm1Sor/Y Nrcam^tm1Gmt/Nrcam^tm1Gmt	involves: 129S6/SvEvTac * 129S7/SvEvBrd * Swiss Webster	MGI:3806032
ot4	L1cam^tm1Sor/Y	either: 129S7/SvEvBrd-L1cam^tm1Sor or (129S7/SvEvBrd * C57BL/6J)F1	MGI:3770650
ot5	L1cam^tm1Sor/Y	involves: 129S7/SvEvBrd	MGI:3770661

Genotype
MGI:3806025

cx1

• Allelic Composition: L1cam^tm1Sor/L1cam⁺; Nrcam^tm1Gmt/Nrcam^tm1Gmt
• Genetic Background: involves: 129S6/SvEvTac * 129S7/SvEvBrd * Swiss Webster

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

mortality/aging

postnatal lethality, incomplete penetrance ( J:71828 )

♀ • increase in rate of postnatal death, especially during the first 1-2 weeks after birth

Genotype
MGI:3806030

cx2

• Allelic Composition: L1cam^tm1Sor/Y; Nrcam^tm1Gmt/Nrcam⁺
• Genetic Background: involves: 129S6/SvEvTac * 129S7/SvEvBrd * Swiss Webster

mortality/aging

postnatal lethality, incomplete penetrance ( J:71828 )

♂ • increase in rate of postnatal death, especially during the first 1-2 weeks after birth

Genotype
MGI:3806032

cx3

• Allelic Composition: L1cam^tm1Sor/Y; Nrcam^tm1Gmt/Nrcam^tm1Gmt
• Genetic Background: involves: 129S6/SvEvTac * 129S7/SvEvBrd * Swiss Webster

Cerebellar abnormalities in L1cam^tm1Sor/Y Nrcam^tm1Gmt/Nrcam^tm1Gmt mice

mortality/aging

postnatal lethality ( J:71828 )

♂ • do not detect any mutants at P8

growth/size/body

decreased body weight ( J:71828 )

♂ • body weights of pups are 40-70% of control littermates at P3-P6

nervous system

abnormal cerebellum development ( J:71828 )

♂ • cerebellar dysgenesis

♂ • cerebellar fissures are less developed

♂ • thickness of the inner granule layer is reduced by 40-50%

abnormal cerebellar foliation ( J:71828 )

♂ • marker analysis indicates defects in foliation

abnormal cerebellum external granule cell layer morphology ( J:71828 )

♂ • thickness of the external granule layer is reduced by 10-30%

abnormal cerebellar cortex morphology ( J:71828 )

♂ • cerebellar lobes are less developed

abnormal cerebellar granule layer morphology ( J:71828 )

♂ • marker analysis indicates possible defects in granule cells during cerebellar development

♂ • thickness of the inner granule layer is reduced by 40-50%

♂ • thickness of the external granule layer is reduced by 10-30%

small cerebellum ( J:71828 )

♂

Genotype
MGI:3770650

ot4

• Allelic Composition: L1cam^tm1Sor/Y
• Genetic Background: either: 129S7/SvEvBrd-L1cam^tm1Sor or (129S7/SvEvBrd * C57BL/6J)F1

mortality/aging

mortality/aging ( J:45013 )

♂N • males survive >18 months

prenatal lethality, incomplete penetrance ( J:45013 )

♂ • males are born at ~40% of expected frequency (84/211 total males)

growth/size/body

decreased body size ( J:45013 )

♂ • initially males are ~60% size of wild-type littermates

slow postnatal weight gain ( J:45013 )

♂ • by adulthood, males attain ~80% the size of wild-type littermates

nervous system

nervous system phenotype ( J:45013 )

♂N • the optic chiasm, corpus callosum, and spinal commissural projection in mutants show normal axonal pathfinding and crossing projections, in contrast to the pyramidal decussation

abnormal axon guidance ( J:45013 )

♂ • in P3-P5 animals, very few corticospinal axons grow to the contralateral dorsal columns at the pyramidal decussation; many axons instead turn ventrally at midline and enter the contralateral pyramid

♂ • in one animal, aberrant axons turn rostrally in contralateral pyramid and project back towards midbrain; in other animals, axons can't be traced beyond decussation

♂ • no axons are apparent caudal to the decussation, either ventrally or dorsally

abnormal corticospinal tract morphology ( J:45013 )

♂ • in adult males examined, corticospinal axons project normally to the medulla, but at the level of the decussation, a substantial portion of axons fail to cross the midline and instead pass ipsilaterally into the dorsal columns

♂ • no axon labeling is detected more caudally than the cervical spinal cord in male mutants

behavior/neurological

abnormal motor capabilities/coordination/movement ( J:45013 )

♂

hindlimb paralysis ( J:45013 )

♂ • dragging of hindlimbs is observed in some mice >12 months of age

reproductive system

reproductive system phenotype ( J:45013 )

♂N • although males are sterile, testis contain germ cells

male infertility ( J:45013 )

♂ • some individuals are able to breed but most are effectively sterile

vision/eye

enophthalmos ( J:45013 )

♂ • adult mutants have sunken eyes

excessive tearing ( J:45013 )

♂ • adult mutants have lacrimous eyes

pigmentation

abnormal coat/hair pigmentation ( J:45013 )

♂ • Background Sensitivity: with age, mice on congenic 129/Sv agouti background develop patches of black fur on their backs

integument

abnormal coat/hair pigmentation ( J:45013 )

♂ • Background Sensitivity: with age, mice on congenic 129/Sv agouti background develop patches of black fur on their backs

long toenails ( J:45013 )

♂ • Background Sensitivity: mice have abnormally long hind-paw toenails (4-5 mm) on congenic 129/Sv background

cellular

abnormal axon guidance ( J:45013 )

♂ • in P3-P5 animals, very few corticospinal axons grow to the contralateral dorsal columns at the pyramidal decussation; many axons instead turn ventrally at midline and enter the contralateral pyramid

♂ • in one animal, aberrant axons turn rostrally in contralateral pyramid and project back towards midbrain; in other animals, axons can't be traced beyond decussation

♂ • no axons are apparent caudal to the decussation, either ventrally or dorsally

limbs/digits/tail

long toenails ( J:45013 )

♂ • Background Sensitivity: mice have abnormally long hind-paw toenails (4-5 mm) on congenic 129/Sv background

Genotype
MGI:3770661

ot5

• Allelic Composition: L1cam^tm1Sor/Y
• Genetic Background: involves: 129S7/SvEvBrd

growth/size/body

decreased body weight ( J:47995 )

♂ • mutants show reduced body weights

nervous system

abnormal axon extension ( J:47995 )

♂ • cultured neurons grown on L1-Fc chimera (molecule of Fc region of human IgG and entire extracellular domain of human L1) show impaired ability to extend neurites compared to wild-type neurons; fewer neurons show outgrowth and extend shorter neurites compared to wild-type neurons

abnormal brain morphology ( J:47995 )

♂ • total brain volume is significantly reduced compared to controls

abnormal fourth ventricle morphology ( J:47995 )

♂ • volume of fourth ventricle is increased compared to controls

enlarged fourth ventricle ( J:47995 )

♂ • volume of fourth ventricle is increased compared to controls

dilated lateral ventricle ( J:47995 )

♂ • significant dilation of lateral ventricles is observed

abnormal cerebral aqueduct morphology ( J:47995 )

♂ • shape is different in mutants; distal part connecting ampulla of aqueduct to fourth ventricle is longer in mutants

abnormal cerebellum morphology ( J:47995 )

♂ • ratio between surface of cerebellum and surface of total brain (in midsagittal sections) is reduced compared to wild-type

♂ • cerebellar volume is significantly reduced compared to controls

cerebellum vermis hypoplasia ( J:47995 )

♂ • average surface area of vermis is reduced compared to controls; ratio of surface area of vermis to cerebral cortex surface area is smaller

♂ • hypoplasia is most prominent in lobule 6; one or two of the three sublobule of lobule 6 are underdeveloped or missing in mutants

abnormal sensory neuron innervation pattern ( J:137627 )

♂ • developing embryos have aberrant projections of sensory afferents in the spinal cord

♂ • significant numbers of aberrant projections from the dorsal funiculus to the dorsal horn are evident at E12.5 compared to virtually none in the wild-type controls

♂ • the number of aberrant projections increase at E13.5 and again at E14.5 and always remain at least 4-fold higher than controls

♂ • by E14.5, the aberrant projections are also greater in length than controls with projections sometimes almost reaching the midline

♂ • the number of aberrant projections is less than what is observed in Cntn2 null homozgyotes

abnormal spinal cord dorsal horn morphology ( J:137627 )

♂ • developing embryos have aberrant projections of sensory afferents from the dorsal funiculus to the dorsal horn

abnormal somatic nervous system physiology ( J:137627 )

♂ • cultured dorsal root ganglion cells have much less repulsion to ventral spinal cord explants than controls

♂ • in culture, E13.5 sensory axons are completely refractory to repulsion mediated by Semaphorin-3A

behavior/neurological

abnormal spatial learning ( J:47995 )

♂ • mutants show impaired spatial learning in Morris water-maze paradigm in probe trials where platform is removed; mutants spend significantly less time in target quadrant and majority of time is localized to periphery

increased thigmotaxis ( J:47995 )

♂ • in open field test, most mutants spend less time exploring, instead running in circles around perimeter of cage

impaired coordination ( J:47995 )

♂ • in rotarod trials, mutants display difficulties in maintaining balance, and fall on at least one attempt, compared to wild-type controls

decreased locomotor activity ( J:47995 )

♂ • mutants show ~50% of total cage activity that is displayed by wild-type controls

abnormal social/conspecific interaction behavior ( J:47995 )

♂ • when a cage containing 2 female mice is placed in center of open field test cage, mutants do not adapt exploration pattern to this external stimulus; mutants still display circling of cage periphery while wild-type spend 45% of their exploratory behavior within 10 cm of the cage

cellular

abnormal axon extension ( J:47995 )

♂ • cultured neurons grown on L1-Fc chimera (molecule of Fc region of human IgG and entire extracellular domain of human L1) show impaired ability to extend neurites compared to wild-type neurons; fewer neurons show outgrowth and extend shorter neurites compared to wild-type neurons