Phenotypes associated with this allele

• Allele Symbol: Lama2^dy
• Allele Name: dystrophia muscularis
• Allele ID: MGI:1856026
• Summary: 7 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Lama2^dy/Lama2^dy	129P1/ReJ-Lama2^dy/J	MGI:3789337
hm2	Lama2^dy/Lama2^dy	B6.129P1-Lama2^dy/J	MGI:3789312
hm3	Lama2^dy/Lama2^dy	involves: 129P1/Re	MGI:3783638
hm4	Lama2^dy/Lama2^dy	involves: 129P1/Re * C57BL/6	MGI:2654138
hm5	Lama2^dy/Lama2^dy	involves: 129P1/ReJ	MGI:3789478
cx6	C3^tm1Hrc/C3^tm1Hrc Lama2^dy/Lama2^dy	either: (involves: 129S2/SvPas * 129P1/ReJ) or (involves: 129X1/SvJ * 129P1/ReJ)	MGI:3789477
cx7	Lama2^dy/Lama2^dy Lama4^tm1Ktry/Lama4^tm1Ktry	involves: 129P1/ReJ * 129X1/SvJ	MGI:3789471

Genotype
MGI:3789337

hm1

• Allelic Composition: Lama2^dy/Lama2^dy
• Genetic Background: 129P1/ReJ-Lama2^dy/J

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

nervous system

decreased brain weight ( J:7911 )

abnormal Schwann cell morphology ( J:12730 )

• after P7, the number of Schwann cell nuclei increases

decreased spinal cord weight ( J:7911 )

demyelination ( J:5331 , J:12730 )

• mice exhibit a 36% decrease in myelinated nerves at the sciatic I level (J:5331)

• in the dorsal and ventral roots of the spinal and cranial peripheral nerves, Schwann cells fail to separate and ensheathe axons so that groups of closely apposed naked axons, normally seen only in early stages, persist into adulthood (J:5331)

• fetal axons of less than 0.5 um diameter lack myelin or Schwann cell ensheathment in the peripheral nervous system (J:12730)

• the onset of myelination is delayed compared to in wild-type mice (J:12730)

• the length of myelinated segments added to an existing population are shorter than in wild-type mice (J:12730)

• myelinated internodal lengths are shorter than in wild-type mice in the peripheral nervous system (J:12730)

abnormal axonal transport ( J:5709 )

• transport of dopamine-beta-hydrolase in nerves is reduced compared to in wild-type mice

homeostasis/metabolism

abnormal lipid level ( J:7911 )

• mice exhibit a reduction in total spinal cord lipid levels and specifically galactolipids and cerebroside sulfatide compared to wild-type mice

• mice exhibit a decrease in total amount of cerebroside sulfatide in the brain compared to wild-type mice

increased cholesterol level ( J:7911 )

• total cholesterol levels in the spinal cord are higher than in wild-type mice

abnormal galactolipid level ( J:7911 )

• total galactolipid levels in the spinal cord are lower than in wild-type mice

growth/size/body

decreased body weight ( J:7911 )

cellular

abnormal basement membrane morphology ( J:5565 , J:5866 )

• the basement membrane of Schwann cells around myelinated axons is gapped whereas it is absent in amyelinated zones (J:5565)

• nodes exhibit unusually long segments bare of basement membrane (J:5565)

• the internodal gap in the basement membrane of peripheral nerves at the nodes of Ranvier is lengthened compared to in wild-type mice (J:5866)

Genotype
MGI:3789312

hm2

• Allelic Composition: Lama2^dy/Lama2^dy
• Genetic Background: B6.129P1-Lama2^dy/J

hearing/vestibular/ear

abnormal bony labyrinth ( J:101670 )

• spaces normally filled with perilymph and endolymph fluids are obliterated with a fibrotic debris

abnormal organ of Corti morphology ( J:101670 )

• the structural integrity of the organ of Corti is altered with supporting and hair cells not exhibiting their normal vertical height and a slight compression of the organ, especially at the apical half turn

abnormal cochlear hair cell morphology ( J:101670 )

• hair cells in the organ of Corti not exhibiting their normal vertical height

absent cochlear hair cells ( J:101670 )

abnormal organ of Corti supporting cell morphology ( J:101670 )

• supporting not exhibiting their normal vertical height

cochlear degeneration ( J:101670 )

stria vascularis degeneration ( J:101670 )

abnormal inner ear vestibule morphology ( J:101670 )

• mice exhibit a degeneration of vestibular structures

absent vestibular hair cells ( J:101670 )

increased or absent threshold for auditory brainstem response ( J:101670 )

• mice exhibit an increase in brainstem auditory threshold compared to wild-type mice

behavior/neurological

abnormal motor capabilities/coordination/movement ( J:101670 )

• mice exhibit impaired motor activity

• however, no circling or head twisting is observed

abnormal motor coordination/balance ( J:5000 )

• mice stumble when walking

nervous system

abnormal cochlear hair cell morphology ( J:101670 )

• hair cells in the organ of Corti not exhibiting their normal vertical height

absent cochlear hair cells ( J:101670 )

absent vestibular hair cells ( J:101670 )

abnormal cochlear nerve morphology ( J:101670 )

• few if any nerve fibers remain in the ear

decreased nerve conduction velocity ( J:5948 )

craniofacial

abnormal cranium morphology ( J:129632 )

• the posterior portion of the skull is slightly expanded while the medial portion is narrowed

• mice exhibit wider braincases, a slight flexion in the middle and rotated mandibles

abnormal bony labyrinth ( J:101670 )

• spaces normally filled with perilymph and endolymph fluids are obliterated with a fibrotic debris

increased cranium width ( J:129632 )

• skull width relative to skull length increase is more pronounced than in Lama2^dy-2J homozygotes

reproductive system

decreased testis weight ( J:5000 )

♂

growth/size/body

decreased body weight ( J:5000 )

• drastic

homeostasis/metabolism

increased circulating prolactin level ( J:5000 )

muscle

muscle weakness ( J:101670 )

endocrine/exocrine glands

decreased testis weight ( J:5000 )

♂

skeleton

abnormal cranium morphology ( J:129632 )

• the posterior portion of the skull is slightly expanded while the medial portion is narrowed

• mice exhibit wider braincases, a slight flexion in the middle and rotated mandibles

abnormal bony labyrinth ( J:101670 )

• spaces normally filled with perilymph and endolymph fluids are obliterated with a fibrotic debris

increased cranium width ( J:129632 )

• skull width relative to skull length increase is more pronounced than in Lama2^dy-2J homozygotes

Genotype
MGI:3783638

hm3

• Allelic Composition: Lama2^dy/Lama2^dy
• Genetic Background: involves: 129P1/Re

mortality/aging

premature death ( J:13125 )

• most homozygotes die between 1 and 6 months of age

muscle

abnormal sarcolemma morphology ( J:13125 )

• unusual proliferation of sarcolemmal nuclei

abnormal skeletal muscle fiber morphology ( J:13125 )

• in contrast to wild-type, space between fibers is increased and an increase in interstitial tissue is observed

• in some cases, fat cells are found between fibers

• unusual proliferation of nuclei both within and between the fibers

• affected fibers appear rounded rather than polygonal in transverse section

increased variability of skeletal muscle fiber size ( J:13125 )

• individual fibers exhibit size variations

centrally nucleated skeletal muscle fibers ( J:13125 )

• some fibers, although otherwise normal, contain long chains of centrally, rather than peripherally, located nuclei

dystrophic muscle ( J:13125 )

• muscular atrophy proceeds from hind quarters to axial and forelimb musculature

progressive muscle weakness ( J:13125 )

• mild paralysis is first observed at 3.5 week and progresses to hindlimb dragging by 8 weeks

• eventually there is a complete loss of locomotor function and premature death

skeleton

kyphosis ( J:13125 )

• observed at 8 weeks

behavior/neurological

ataxia ( J:13125 )

• ataxia with occasional unilateral paresis is first observed at 3.5 weeks of age

paresis ( J:13125 )

• unilateral paresis begins at 3.5 weeks progressing to bilateral paresis

• paresis is accompanied by spasmodic flexion and flaccid extension in hindlimbs

• mild paralysis is first observed at 3.5 weeks and progresses to hindlimb dragging by 8 weeks

abnormal sexual interaction ( J:13125 )

• failure to mate putatively due to physical disability

• gonad morphology is normal

growth/size/body

decreased body weight ( J:13125 )

• by two weeks of age, body weight is less than wildtype

• weight difference continues through out lifespan

cachexia ( J:13125 )

• cachexia as well as thinning and ruffling of fur is observed by 8 weeks

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
congenital merosin-deficient muscular dystrophy 1A		DOID:0110636	OMIM:607855	J:13125

Genotype
MGI:2654138

hm4

• Allelic Composition: Lama2^dy/Lama2^dy
• Genetic Background: involves: 129P1/Re * C57BL/6

muscle

abnormal skeletal muscle fiber morphology ( J:152525 )

• only a few necrotic fibers are found at 10 days of age but by 15 days of age there are necrotic fibers undergoing phagocytosis and fibers with internal nuclei and by 20 days of age there is an increase in both the number of necrotic and regenerating fibers and a variability in the muscle fiber size

increased variability of skeletal muscle fiber size ( J:134367 , J:152525 )

• mutant muscles contain myofibers of different calibers with increased fiber loss and the presence of fibrotic lesions (J:134367)

• evident by 15 days of age (J:152525)

centrally nucleated skeletal muscle fibers ( J:152525 )

decreased skeletal muscle fiber number ( J:152525 )

• the total number of muscle fibers in the soleus is decreased after 15 days of age

skeletal muscle fiber necrosis ( J:152525 )

skeletal muscle interstitial fibrosis ( J:134367 , J:152525 )

• proliferation of interstitial tissue is found skeletal muscle by 20 days of age (J:152525)

impaired skeletal muscle regeneration ( J:134367 )

• mice exhibit a decreased regenerative capacity with a reduction of total fiber number and a decrease in centrally localized nuclei compared to in wild-type mice

myopathy ( J:134367 )

nervous system

abnormal myelination ( J:134367 )

• peripheral nerve roots in the spine exhibit severe hypomyelination

• despite adherence of Schwann cells to axons and extension of processes, myelination is not completed

cellular

abnormal basal lamina morphology ( J:134367 )

• the basal lamina of muscles is discontinuous, sparse and enmeshed with collagen fibrils from the collapse of the reticular lamina

• the basal lamina of Schwann cells is sparse

• the basal lamina was absent from non-myelinating Schwann cells

Genotype
MGI:3789478

hm5

• Allelic Composition: Lama2^dy/Lama2^dy
• Genetic Background: involves: 129P1/ReJ

mortality/aging

premature death ( J:102959 )

• only 66% of mice survive the 24 week experiment compared to 86% of C3^tm1Hrc Lama2^dy homozygotes

muscle

skeletal muscle interstitial fibrosis ( J:102959 )

dystrophic muscle ( J:102959 )

abnormal muscle physiology ( J:102959 )

• mice display hindlimb contractures

muscle weakness ( J:102959 )

• forelimb strength is decreased compared to in C3^tm1Hrc Lama2^dy homozygotes

growth/size/body

postnatal growth retardation ( J:102959 )

• compared to C3^tm1Hrc Lama2^dy homozygotes

immune system

increased IgG level ( J:102959 )

• mice exhibit increased deposition of IgG in muscles compared to in wild-type mice

increased IgM level ( J:102959 )

• mice exhibit increased deposition of IgM in muscles compared to in wild-type mice and C3^tm1Hrc Lama2^dy homozygotes

skeleton

scoliosis ( J:102959 )

• unlike C3^tm1Hrc Lama2^dy homozygotes

hematopoietic system

increased IgG level ( J:102959 )

• mice exhibit increased deposition of IgG in muscles compared to in wild-type mice

increased IgM level ( J:102959 )

• mice exhibit increased deposition of IgM in muscles compared to in wild-type mice and C3^tm1Hrc Lama2^dy homozygotes

Genotype
MGI:3789477

cx6

• Allelic Composition: C3^tm1Hrc/C3^tm1Hrc; Lama2^dy/Lama2^dy
• Genetic Background: either: (involves: 129S2/SvPas * 129P1/ReJ) or (involves: 129X1/SvJ * 129P1/ReJ)

mortality/aging

extended life span ( J:102959 )

• 86% of mice survive the 24 week experiment compared to only 66% of Lama2^dy homozygotes

muscle

abnormal skeletal muscle morphology ( J:102959 )

• fewer macrophages are found within muscles compared to in Lama2^dy homozygotes

skeletal muscle interstitial fibrosis ( J:102959 )

dystrophic muscle ( J:102959 )

behavior/neurological

abnormal physical strength ( J:102959 )

• mice exhibit 25% to 20% greater forelimb strength than Lama2^dy homozygotes

growth/size/body

increased body weight ( J:102959 )

• compared to Lama2^dy homozygotes

immune system

increased IgG level ( J:102959 )

• mice exhibit increased deposition of IgG in muscles compared to in wild-type mice

decreased IgM level ( J:102959 )

• mice exhibit reduce deposition of IgM in muscles compared to in Lama2^dy homozygotes

increased IgM level ( J:102959 )

• mice exhibit increased deposition of IgM in muscles compared to in wild-type mice

hematopoietic system

increased IgG level ( J:102959 )

• mice exhibit increased deposition of IgG in muscles compared to in wild-type mice

decreased IgM level ( J:102959 )

• mice exhibit reduce deposition of IgM in muscles compared to in Lama2^dy homozygotes

increased IgM level ( J:102959 )

• mice exhibit increased deposition of IgM in muscles compared to in wild-type mice

Genotype
MGI:3789471

cx7

• Allelic Composition: Lama2^dy/Lama2^dy; Lama4^tm1Ktry/Lama4^tm1Ktry
• Genetic Background: involves: 129P1/ReJ * 129X1/SvJ

nervous system

abnormal rostral migratory stream morphology ( J:120076 )

• the rostral migratory stream is less compact than in wild-type mice and cells do not form chains as in wild-type mice