Phenotypes associated with this allele

• Allele Symbol: Lama2^tm1Eeng
• Allele Name: targeted mutation 1, Eva Engvall
• Allele ID: MGI:3522319
• Summary: 6 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Lama2^tm1Eeng/Lama2^tm1Eeng	involves: 129S1/Sv	MGI:4947712
hm2	Lama2^tm1Eeng/Lama2^tm1Eeng	involves: 129S1/Sv * Black Swiss	MGI:3522483
hm3	Lama2^tm1Eeng/Lama2^tm1Eeng	involves: 129S1/Sv * Black Swiss * FVB/N	MGI:3522485
cn4	Lama2^tm1Eeng/Lama2^tm1Eeng Smdt1^tm1c(EUCOMM)Wtsi/Smdt1^tm1c(EUCOMM)Wtsi Tg(Ckmm-cre)5Khn/0	involves: 129S1/Sv * 129S4/SvJae * C57BL/6N * FVB	MGI:6458049
cx5	Bax^tm1Sjk/Bax^tm1Sjk Lama2^tm1Eeng/Lama2^tm1Eeng	B6.129-Bax^tm1Sjk Lama2^tm1Eeng	MGI:3789336
cx6	Lama2^tm1Eeng/Lama2^tm1Eeng Tg(Myod1-BCL2)1Jbm/?	B6.Cg-Lama2^tm1Eeng Tg(Myod1-BCL2)1Jbm	MGI:3789481

Genotype
MGI:4947712

hm1

• Allelic Composition: Lama2^tm1Eeng/Lama2^tm1Eeng
• Genetic Background: involves: 129S1/Sv

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

mortality/aging

premature death ( J:170192 )

perinatal lethality, incomplete penetrance ( J:170192 )

• some newborn death is observed

muscle

myositis ( J:170192 )

• inflammation is seen in muscles, with macrophage infiltration in foci of TN-C expression in mutant muscle and induction of TNFalpha and IL-1beta

dystrophic muscle ( J:170192 )

muscle degeneration ( J:170192 )

• necrotic muscle cell death

muscle weakness ( J:170192 )

• hindlimb weakness is evident by 2 to 3 weeks of age

• inward contraction and slight tremors of hindlimbs are seen when mutants are suspended

• hindlimb fatigue and dragging are seen at later stages

growth/size/body

decreased body size ( J:170192 )

• small size is seen by 7 days of age

behavior/neurological

hindlimb paralysis ( J:170192 )

• hindlimb paralysis and rigid contractures occur in mutants surviving past 8 weeks of age

immune system

myositis ( J:170192 )

• inflammation is seen in muscles, with macrophage infiltration in foci of TN-C expression in mutant muscle and induction of TNFalpha and IL-1beta

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
congenital merosin-deficient muscular dystrophy 1A		DOID:0110636	OMIM:607855	J:170192

Genotype
MGI:3522483

hm2

• Allelic Composition: Lama2^tm1Eeng/Lama2^tm1Eeng
• Genetic Background: involves: 129S1/Sv * Black Swiss

muscle

dystrophic muscle ( J:59089 )

• 1 month old skeletal muscle showed fiber necrosis and fibrosis, indicating muscle degeneration and developed muscular dystrophy at 2-3 weeks of age

impaired skeletal muscle regeneration ( J:59089 )

• skeletal muscle was unable to complete regeneration in response to injury

• low incidence of new myotube formation

• newly formed myofibers undergo apoptosis

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
congenital merosin-deficient muscular dystrophy 1A		DOID:0110636	OMIM:607855	J:59089

Genotype
MGI:3522485

hm3

• Allelic Composition: Lama2^tm1Eeng/Lama2^tm1Eeng
• Genetic Background: involves: 129S1/Sv * Black Swiss * FVB/N

mortality/aging

premature death ( J:49435 )

• most die within 2-4 weeks after birth though a few survive up to 3-4 months

postnatal lethality, incomplete penetrance ( J:49435 )

• most die within 2-4 weeks after birth though a few survive up to 3-4 months

behavior/neurological

decreased aggression ( J:49435 )

• homozygotes were passive

limb grasping ( J:49435 )

• from 2-3 weeks of age, flexed hind legs to the trunk when lifted by the tail

hindlimb paralysis ( J:49435 )

• hindlimbs become increasingly paralyzed with age

growth/size/body

decreased body size ( J:49435 )

• 1 and 3 month old mutants are smaller and thinner than wild-type

decreased body weight ( J:49435 )

muscle

dystrophic muscle ( J:49435 )

• showed extensive muscle degeneration, muscle fiber necrosis and pronounced fibrosis

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
congenital merosin-deficient muscular dystrophy 1A		DOID:0110636	OMIM:607855	J:49435

Genotype
MGI:6458049

cn4

• Allelic Composition: Lama2^tm1Eeng/Lama2^tm1Eeng; Smdt1^{tm1c(EUCOMM)Wtsi}/Smdt1^{tm1c(EUCOMM)Wtsi}; Tg(Ckmm-cre)5Khn/0
• Genetic Background: involves: 129S1/Sv * 129S4/SvJae * C57BL/6N * FVB

mortality/aging

premature death ( J:287405 )

• as in Lama2^tm1Eeng homozygotes

behavior/neurological

decreased grip strength ( J:287405 )

• as in Lama2^tm1Eeng homozygotes

cellular

abnormal mitochondrial physiology ( J:287405 )

• increase in mitochondrial calcium in skeletal muscle fiber as in Lama2^tm1Eeng homozygotes

Genotype
MGI:3789336

cx5

• Allelic Composition: Bax^tm1Sjk/Bax^tm1Sjk; Lama2^tm1Eeng/Lama2^tm1Eeng
• Genetic Background: B6.129-Bax^tm1Sjk Lama2^tm1Eeng

mortality/aging

extended life span ( J:94431 )

• early death found in Lama2 mutant homozygotes is prevented by the homozygous presence of the Bax disruption, survival exceeds 120 days

muscle

abnormal skeletal muscle fiber morphology ( J:94431 )

increased skeletal muscle mass ( J:94431 )

• individual muscles are larger, in both mass and cross-sectional area, and have more myofibers than those wild-type for Bax

impaired skeletal muscle regeneration ( J:94431 )

• the abnormal muscle regeneration of Lama2 mutants is not rescued by the Bax disruption

growth/size/body

abnormal postnatal growth/weight/body size ( J:94431 )

• inactivation of Bax results in increased weight gain and growth relative to Bax wild-type Lama2 mutants, but inactivation of Bax does not entirely rescue Lama2 mutants from diminished weight gain and growth

decreased body size ( J:94431 )

decreased body weight ( J:94431 )

behavior/neurological

behavior/neurological phenotype ( J:94431 )

N • the hindlimb fixed contractures found in Lama2 mutants are prevented by the disruption of Bax such that even at 6 months of age the hindlimbs, although weaker than in wild-type, are not paralyzed and there is normal exploratory standing behavior

Genotype
MGI:3789481

cx6

• Allelic Composition: Lama2^tm1Eeng/Lama2^tm1Eeng; Tg(Myod1-BCL2)1Jbm/?
• Genetic Background: B6.Cg-Lama2^tm1Eeng Tg(Myod1-BCL2)1Jbm

mortality/aging

extended life span ( J:94431 )

• early death found in Lama2 homozygotes is prevented by this transgenic restricted expression of human BCL2 in skeletal muscle, survival exceeds 90 days in all of 6 mice and half lived longer than 120 days

growth/size/body

abnormal postnatal growth/weight/body size ( J:94431 )

• transgenic expression of BCL2 results in increased weight gain and growth rate relative to non-transgenic Lama2 mutants, but does not entirely rescue Lama2 mutants from diminished weight gain and growth