Phenotypes associated with this allele

• Allele Symbol: Col13a1^tm3.1Pih
• Allele Name: targeted mutation 3.1, Taina Pihlajaniemi
• Allele ID: MGI:4838409
• Summary: 2 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Col13a1^tm3.1Pih/Col13a1^tm3.1Pih	involves: 129S1/Sv * 129X1/SvJ	MGI:6316981
hm2	Col13a1^tm3.1Pih/Col13a1^tm3.1Pih	involves: 129S1/Sv * 129X1/SvJ * C57BL/6	MGI:4838425

Genotype
MGI:6316981

hm1

• Allelic Composition: Col13a1^tm3.1Pih/Col13a1^tm3.1Pih
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ

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

growth/size/body

postnatal growth retardation ( J:242846 )

• reduced body weight at puberty and when aging but not in adulthood

muscle

abnormal soleus morphology ( J:242846 )

• the soleus muscle is smaller in size at P84

decreased soleus weight ( J:242846 )

• soleus muscle weight is decreased at P84 but is similar to wild-type mice at the onset of neuromuscular junction maturity at P28

abnormal skeletal muscle fiber morphology ( J:242846 )

• increase in proportion of small muscle fibers and a slight increase in number of centrally located nuclei both in the diaphragm and soleus, indicating muscle regeneration

• small muscle fibers are scattered and angular in shape in the soleus muscle

skeletal muscle fiber atrophy ( J:242846 )

• progressive atrophy of the slow muscle fibers in the soleus

centrally nucleated skeletal muscle fibers ( J:242846 )

• slight increase in the number of centrally located nuclei both in the diaphragm and soleus

abnormal diaphragm morphology ( J:242846 )

• the diaphragm is pressed deeper towards the thoracic cavity

abnormal skeletal muscle fiber type ratio ( J:242846 )

• marker analysis indicates a shift in the muscle fiber type distribution towards fast/mixed at the expense of slow muscle fibers in the soleus but not diaphragm

muscle weakness ( J:242846 )

♂ • males show a reduced grid hanging time indicating muscle weakness

♂ • males treated with 3,4-diaminopyridine show improved grid hanging time

nervous system

abnormal motor neuron morphology ( J:242846 )

• terminal branching complexity of motor axons is decreased, with decreased level of terminal divisions as well as number of terminal branches and tips

abnormal neuromuscular synapse morphology ( J:242846 )

• neuromuscular synapses do not reach full size, alignment or complexity

• acetylcholine receptor clusters remain small and immature in neuromuscular junction, with cluster size decreased by 33% and 41% in P28 and P84 mice

• the acetylcholine-containing vesicles do not exclusively accumulate at the nerve terminus even at P84, but are also seen in the pre-terminal axon

• active zone numbers are reduced in neuromuscular junctions

cellular

abnormal endocytosis ( J:242846 )

• endocytosis is decreased in the nerve termini in the diaphragm

limbs/digits/tail

abnormal soleus morphology ( J:242846 )

• the soleus muscle is smaller in size at P84

decreased soleus weight ( J:242846 )

• soleus muscle weight is decreased at P84 but is similar to wild-type mice at the onset of neuromuscular junction maturity at P28

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
congenital myasthenic syndrome 19		DOID:0110673	OMIM:616720	J:242846

Genotype
MGI:4838425

hm2

• Allelic Composition: Col13a1^tm3.1Pih/Col13a1^tm3.1Pih
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6

nervous system

abnormal neuromuscular synapse morphology ( J:164671 )

• mice exhibit abnormal acetylcholine receptor clusters in the postsynaptic membrane compared with wild-type

• presynaptic defects include a failure of synaptic vesicles to properly cluster in the nerve terminal and remain in axons, nerve terminals that fail to fully cover acetylcholine receptor clusters, and synaptic vesicle-rich sprouts that extend beyond the border of the postsynaptic specialization unlike in wild-type mice

• neuromuscular junctions exhibit erroneously enwrapped nerve terminals and decreased contact surface for neurotransmission compared to in wild-type mice

• at P14, acetylcholine receptor clusters are smaller than in wild-type and remain unperforated and unbranched unlike in wild-type mice

• at P28 and P56, acetylcholine receptor clusters remain small, simple, and plaque-like unlike in wild-type mice

abnormal synaptic vesicle morphology ( J:164671 )

• presynaptic defects include a failure of synaptic vesicles to properly cluster in the nerve terminal and remain in axons unlike in wild-type mice

abnormal endplate potential ( J:164671 )

• motor nerves elicit slightly reduced postsynaptic endplate potential compared to in wild-type mice

• paired-pulse stimulation with interstimulus intervals of 30 ms induces depression unlike in similarly treated wild-type mice

abnormal miniature endplate potential ( J:164671 )

• mice exhibit slightly reduced miniature endplate potential (MEPP) amplitude and dramatically reduced MEPP frequency compared to in wild-type mice

abnormal synaptic acetylcholine release ( J:164671 )

• enhanced acetylcholine quantal release induced by sucrose or potassium is compromised compared to in wild-type mice

behavior/neurological

tremors ( J:164671 )

growth/size/body

postnatal growth retardation ( J:164671 )

• while mice exhibit normal weights at birth and in adulthood, mice exhibit slow grow at puberty compared with wild-type mice