Phenotypes associated with this allele

• Allele Symbol: Papss2^bm
• Allele Name: brachymorphic
• Allele ID: MGI:1856688
• Summary: 6 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Papss2^bm/Papss2^bm	B6C3Fe a/a-Papss2^bm/J	MGI:3707358
hm2	Papss2^bm/Papss2^bm	involves: C57BL/6J * LDJ/Le	MGI:4457408
hm3	Papss2^bm/Papss2^bm	involves: LDJ/LeJ	MGI:4839540
hm4	Papss2^bm/Papss2^bm	LDJ/Le	MGI:3054675
cx5	Bpnt2^Gt(RST634)Byg/Bpnt2^Gt(RST634)Byg Papss2^bm/Papss2^bm	involves: 129P2/OlaHsd * LDJ/Le	MGI:5494467
cx6	Bpnt1^tm1Yrk/Bpnt1^tm1Yrk Papss2^bm/Papss2^bm	involves: 129S/SvEv * C57BL/6 * LDJ/Le	MGI:5494469

Genotype
MGI:3707358

hm1

• Allelic Composition: Papss2^bm/Papss2^bm
• Genetic Background: B6C3Fe a/a-Papss2^bm/J

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

homeostasis/metabolism

increased bleeding time ( J:31800 )

• bleeding time is increased 2.6- to 3-fold compared to controls

• platelet numbers and function appear normal

skeleton

abnormal long bone epiphyseal plate morphology ( J:166505 )

abnormal long bone epiphyseal plate proliferative zone ( J:166505 )

• Background Sensitivity: proliferative zone of the upper tibia at 16 and 25 days of age is reduced in height and has irregular cell columns with some areas distinctly disorganized and others fairly normal

abnormal long bone hypertrophic chondrocyte zone ( J:166505 )

• the pattern of hypertrophic cells in the hypertrophic zone of tibiae from 16 and 25 day old homozygotes is severely disturbed with most of the cells polygonal and irregularly shaped and often containing pyknotic nuclei, and the lacunar matrix being dense and ill-defined

• electron micrographs of the hypertrophic zones at 16 days of age shows matrix vesicles and fibrous structures in the lacuna that are not present in controls

abnormal cartilage development ( J:5640 )

• assessment at 5 days of age reveals undersulfated glycosaminoglycans in the epiphyses of the distal femoral head and proximal tibial head

abnormal chondrocyte morphology ( J:166505 )

• many of the chondrocytes from upper tibia of 16 and 25 day old homozygotes are irregular in shape with pycnotic nuclei and this is more pronounced in the distal portion of the proliferative zone

• electron micrographs of hypertrophic and proliferative chondrocytes show morphological abnormalities including distention of the endoplasmic reticular cisternae

chondrodystrophy ( J:5640 )

abnormal endochondral bone ossification ( J:166505 )

• the pattern of mineralization in tibial proximal epiphyseal plate is irregular and patchy, cells of the mineralization zone have pyknotic nuclei and lack the normal cytoplasic vacuolization, and, distinct from controls, type V collagen is found in this cartilage and the fine fibrils of the lacunar matrix lack the typical collagen periodicity

Genotype
MGI:4457408

hm2

• Allelic Composition: Papss2^bm/Papss2^bm
• Genetic Background: involves: C57BL/6J * LDJ/Le

growth/size/body

disproportionate dwarf ( J:5801 )

• homozygotes have a disproportionately short stature with shortened long bones and shortened tails

craniofacial

domed cranium ( J:5801 )

skeleton

domed cranium ( J:5801 )

autoimmune arthritis ( J:166514 )

• severe degenerative knee joint disease is found at 12 months of age in both males and females

abnormal long bone epiphyseal plate morphology ( J:5801 )

• at 5 days of age there is a reduction in size in each zone of tibial and femoral epiphyseal cartilage growth, wih the tibial cartilaginous epiphyseal plate from synovial space to metaphysis only 81% of normal size, and by 16 days of age the epiphyseal plate is only 44 to 67% of normal size with both the columnar and hypertrophic zones markedly reduced in size, notably the hypertrophic region is often only 3 to 4 cells in height at 16 days of age

• the growth plate is abnormally straight

abnormal long bone epiphyseal plate proliferative zone ( J:5801 )

decreased width of hypertrophic chondrocyte zone ( J:5801 )

decreased long bone epiphyseal plate size ( J:5801 )

abnormal cartilage development ( J:6468 )

• analysis of glycosaminoglycans from mesenchymal cultures of embryonic day 11 limb buds reveals significant undersulphation of chondroitin sulfate

immune system

autoimmune arthritis ( J:166514 )

• severe degenerative knee joint disease is found at 12 months of age in both males and females

Genotype
MGI:4839540

hm3

• Allelic Composition: Papss2^bm/Papss2^bm
• Genetic Background: involves: LDJ/LeJ

skeleton

abnormal skeleton development ( J:5934 )

• the length of femora and tibiae is shorter than normal in pre-wean homozygotes and growth is severely interupted at weaning, between 21 and 28 days of age, before resuming slow growth

abnormal long bone epiphyseal plate morphology ( J:166506 )

• at 3 weeks of age and more severe at 6 weeks of age many of the tibial and femural proliferating chondrocytes have pyknotic nuclei, there is a complete disarrangement of the columnar pattern, the primary spongiosa is disorderly and the primary spicules are stubby

abnormal long bone epiphyseal plate proliferative zone ( J:166506 )

• at 3 weeks of age the tibial and femural growth zones are narrow and the columnar pattern is irregular due to a mild increase in intercolumnar matrix

abnormal bone ossification ( J:166506 )

• endochondral ossification has failed chondrocyte hypertrophy and disorientation of the cartilage closest to the metaphysis

abnormal chondrocyte physiology ( J:166506 )

• chondrocytes fail to undergo hypertrophy and to deposit glycogen

Genotype
MGI:3054675

hm4

• Allelic Composition: Papss2^bm/Papss2^bm
• Genetic Background: LDJ/Le

Abnormal skeletal development of Papss2^bm/Papss2^bm (right) mice at P0, P10 and P3

mortality/aging

premature death ( J:5109 )

• a few mutants die from malocclusion

craniofacial

decreased cranium height ( J:5109 )

• skull length is 89% of normal

malocclusion ( J:5109 )

• in some cases leads to death

domed cranium ( J:5109 )

• short, domed skull

cleft palate ( J:15031 )

• increased sensitivity to hydrocortisone induced development of cleft palate

• at E14 palate development was 8 to 12 hours behind normal even without experimental intervention

digestive/alimentary system

abnormal digestive system morphology ( J:5109 )

• at 30 days of age the gut length was 91% of normal

• by 60 days of age, gut length was normal

cleft palate ( J:15031 )

• increased sensitivity to hydrocortisone induced development of cleft palate

• at E14 palate development was 8 to 12 hours behind normal even without experimental intervention

growth/size/body

malocclusion ( J:5109 )

• in some cases leads to death

cleft palate ( J:15031 )

• increased sensitivity to hydrocortisone induced development of cleft palate

• at E14 palate development was 8 to 12 hours behind normal even without experimental intervention

decreased body length ( J:5109 )

• body length is 90% of normal

abnormal body weight ( J:5109 )

• organ weights at 30 days of age about 70-76% normal

• at 60 days of age organ weights varied between 78 and 140% of normal

postnatal growth retardation ( J:5109 )

• retarded growth rate during first 4 weeks of life

• eventually attain near normal body weight

• body length about 90% normal

limbs/digits/tail

abnormal tail morphology ( J:5109 )

short tail ( J:5109 )

• tail length is about 69% of normal

thick tail ( J:5109 )

skeleton

decreased cranium height ( J:5109 )

• skull length is 89% of normal

malocclusion ( J:5109 )

• in some cases leads to death

domed cranium ( J:5109 )

• short, domed skull

abnormal long bone epiphyseal plate morphology ( J:49338 )

abnormal long bone epiphyseal plate proliferative zone ( J:5109 )

• proliferating cartilage cell columns are shorter

decreased width of hypertrophic chondrocyte zone ( J:5109 )

decreased long bone epiphyseal plate size ( J:5109 )

• thinner epiphyseal plates

decreased length of long bones ( J:5109 , J:49338 )

• limb bones from 63 to 86% of normal length (J:5109)

abnormal trabecular bone morphology ( J:5109 )

• primary trabeculae are shorter, less numerous, and not aligned as well as in controls

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
spondyloepimetaphyseal dysplasia, Pakistani type		DOID:0050812	OMIM:612847	J:5109

Genotype
MGI:5494467

cx5

• Allelic Composition: Bpnt2^{Gt(RST634)Byg}/Bpnt2^{Gt(RST634)Byg}; Papss2^bm/Papss2^bm
• Genetic Background: involves: 129P2/OlaHsd * LDJ/Le

mortality/aging

neonatal lethality, complete penetrance ( J:194247 )

• presence of homozygous Papss2^bm does not rescue neonatal lethality or skeletal abnormalities

craniofacial

shortened head ( J:194247 )

limbs/digits/tail

short humerus ( J:194247 )

short radius ( J:194247 )

short ulna ( J:194247 )

short limbs ( J:194247 )

skeleton

short humerus ( J:194247 )

short radius ( J:194247 )

short ulna ( J:194247 )

disorganized long bone epiphyseal plate ( J:194247 )

short scapula ( J:194247 )

abnormal thoracic cage morphology ( J:194247 )

short sternum ( J:194247 )

short ribs ( J:194247 )

axial skeleton hypoplasia ( J:194247 )

abnormal cartilage development ( J:194247 )

growth/size/body

shortened head ( J:194247 )

Genotype
MGI:5494469

cx6

• Allelic Composition: Bpnt1^tm1Yrk/Bpnt1^tm1Yrk; Papss2^bm/Papss2^bm
• Genetic Background: involves: 129S/SvEv * C57BL/6 * LDJ/Le

liver/biliary system

liver/biliary system phenotype ( J:194247 )

N • no hepatotoxicity

N • hepatocytes appear normal

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:194247 )

N • no unusual edema

N • rescued serum chemistry