Phenotypes associated with this allele

• Allele Symbol: Nppc^lbab
• Allele Name: long bone abnormality
• Allele ID: MGI:2388899
• Summary: 4 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Nppc^lbab/Nppc^lbab	B6.PL-Nppc^lbab/GrsrJ	MGI:3707539
hm2	Nppc^lbab/Nppc^lbab	either: (involves: C57BL/6J * PL/J) or PL/J	MGI:2388917
hm3	Nppc^lbab/Nppc^lbab	involves: PL/J	MGI:4365535
cx4	Nppc^lbab/Nppc^lbab Tg(Col2a1-Nppc)1Yog/0	involves: C57BL/6J * PL/J	MGI:7276255

Genotype
MGI:3707539

hm1

• Allelic Composition: Nppc^lbab/Nppc^lbab
• Genetic Background: B6.PL-Nppc^lbab/GrsrJ

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

Nppc^lbab/Nppc^lbab(left) with littermate Nppc^lbab/⁺ (right)

mortality/aging

postnatal lethality, complete penetrance ( J:122924 )

• die before 7 days of age

skeleton

abnormal long bone epiphyseal plate proliferative zone ( J:321139 )

• thickness of the proliferative chondrocyte layer is decreased at 2 weeks of age

• the number of PCNA+ cells is severely decreased in the proliferative chondrocyte layer of the growth plate

decreased width of hypertrophic chondrocyte zone ( J:321139 )

• the hypertrophic chondrocyte layer is thinner at 3 days of age and 2 weeks of age

decreased long bone epiphyseal plate size ( J:321139 )

• the tibial growth plate, especially the hypertrophic chondrocyte layer, is thinner at 3 days of age and is thinner at 10 weeks of age

decreased bone volume ( J:321139 )

decreased trabecular bone thickness ( J:321139 )

• reduction in trabecular thickness of the humerus at 10 weeks of age

abnormal endochondral bone ossification ( J:321139 )

• mice show impaired growth of bones formed through endochondral ossification; longitudinal growth of the vertebrae, tail, and extremities is affected at 2 weeks of age

• in organ culture, fetal tibial explants are shorter than controls

growth/size/body

decreased body size ( J:321139 )

• severe dwarfism

decreased body weight ( J:122924 , J:321139 )

• body weight is 44.1% of wild-type (J:122924)

• body weight is 68% of wild-type at birth and decreases to 46% by 3 weeks of age, but increases after 5 weeks of age, becoming about 60% after 7 weeks (J:321139)

decreased body length ( J:122924 , J:321139 )

• body length is 61.6% of wild-type (J:122924)

• pups are slightly shorter at birth (J:321139)

• the nasoanal and nose-tail lengths are 88 and 83% of those of wild-type, respectively, at birth and decrease to 65% and 55% by the age of 3 weeks, and stabilize at 66-72% and 57-62%, respectively, after 5 weeks of age (J:321139)

disproportionate dwarf ( J:122924 )

limbs/digits/tail

short limbs ( J:122924 )

reproductive system

abnormal female meiosis ( J:164870 )

♀ • while oocytes in late antral follicles are usually maintained at the germinal vesicle stage with arrested meiosis, half of those in homozygotes have already resumed meiosis

cellular

abnormal female meiosis ( J:164870 )

♀ • while oocytes in late antral follicles are usually maintained at the germinal vesicle stage with arrested meiosis, half of those in homozygotes have already resumed meiosis

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
achondroplasia		DOID:4480	OMIM:100800	J:122924
osteochondrodysplasia		DOID:2256		J:321139

Genotype
MGI:2388917

hm2

• Allelic Composition: Nppc^lbab/Nppc^lbab
• Genetic Background: either: (involves: C57BL/6J * PL/J) or PL/J

endocrine/exocrine glands

small testis ( J:79175 )

♂ • one month old homozygous males have exceptionally small testes

growth/size/body

decreased body size ( J:79175 )

• overall smaller body size than their littermates; proportionate dwarfing of all organs with the possible exception of the male reproductive tract

disproportionate dwarf ( J:79175 )

• two mutants examined at 9 weeks of age exhibited a greater long bone: spine proportionality ratio than younger mice, suggesting that the long bones had ceased growing (progressive dwarfism)

limbs/digits/tail

short fibula ( J:79175 )

• long bones are shorter than normal

short tibia ( J:79175 )

• long bones are shorter than normal

short tail ( J:79175 )

• mutants have proportionately shortened tails

reproductive system

reproductive system phenotype ( J:79175 )

N • mature mutant males breed, and testes appear by palpation to be of normal size; testis biopsy of a homozygous male revealed normal sperm heads and many sperm tails

small testis ( J:79175 )

♂ • one month old homozygous males have exceptionally small testes

skeleton

abnormal long bone epiphyseal plate morphology ( J:79175 )

• about 50% of those examined had growth plate abnormalities, while the rest exhibited normal growth plates

• Background Sensitivity: the growth plates are less affected on C57BL/6J than on the original PL/J background

disorganized long bone epiphyseal plate ( J:79175 )

• of those having abnormalities, some showed disorganization of both femoral and tibial growth plates while others of only the femoral growth plates;

decreased length of long bones ( J:79175 )

short fibula ( J:79175 )

• long bones are shorter than normal

short tibia ( J:79175 )

• long bones are shorter than normal

Genotype
MGI:4365535

hm3

• Allelic Composition: Nppc^lbab/Nppc^lbab
• Genetic Background: involves: PL/J

nervous system

abnormal sensory neuron innervation pattern ( J:153212 )

• unlike in wild-type mice, axons entering the spinal cord and turn either in rostral or caudal directions without leaving the funiculus

Genotype
MGI:7276255

cx4

• Allelic Composition: Nppc^lbab/Nppc^lbab; Tg(Col2a1-Nppc)1Yog/0
• Genetic Background: involves: C57BL/6J * PL/J

growth/size/body

decreased body weight ( J:321139 )

• body weight is decreased until 3 weeks of age but then promptly increases to wild-type levels

decreased body length ( J:321139 )

• the nasoanal length is smaller at the first week after birth, however subsequently mice begin to grow and catch up with wild-type mice after 4 weeks of age

skeleton

skeleton phenotype ( J:321139 )

N • the impaired growth of bones formed through endochondral ossification seen in Nppc^lbab mice is partially recovered at 2 weeks of age and almost completely recovered by 10 weeks of age and the reduction in bone volume and trabecular thickness of humerus seen in single Nppc^lbab homozygotes is rescued

decreased width of hypertrophic chondrocyte zone ( J:321139 )

• the thinner hypertrophic chondrocyte layer is considerably recovered but not completely

• however, proliferative chondrocyte layer is normal and tibial growth plate thickness is normal at 10 weeks of age