Phenotypes associated with this allele

• Allele Symbol: Pthlh^tm1Ack
• Allele Name: targeted mutation 1, Andrew C Karaplis
• Allele ID: MGI:2387462
• Summary: 4 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cn1	Pthlh^tm1Ack/Pthlh^tm1Hmk Tmem163^Tg(ACTB-cre)2Mrt/0	involves: 129 * BALB/c * FVB/N	MGI:3617820
cn2	Pthlh^tm1Ack/Pthlh^tm1Hmk Tg(LGB-cre)74Acl/0	involves: 129 * C57BL/6 * CBA	MGI:3617822
cn3	Pthlh^tm1Ack/Pthlh^tm1.1Ack Tmem163^Tg(ACTB-cre)2Mrt/0	involves: 129S1/Sv * 129X1/SvJ * BALB/c * FVB/N	MGI:3617821
cn4	Pthlh^tm1Ack/Pthlh^tm1Ack Tg(Col1a1-cre)1Ack/0	involves: 129S1/Sv * 129X1/SvJ * FVB/N	MGI:3617818

Genotype
MGI:3617820

cn1

• Allelic Composition: Pthlh^tm1Ack/Pthlh^tm1Hmk; Tmem163^{Tg(ACTB-cre)2Mrt}/0
• Genetic Background: involves: 129 * BALB/c * FVB/N

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

mortality/aging

neonatal lethality, complete penetrance ( J:69396 )

skeleton

short mandible ( J:69396 )

domed cranium ( J:69396 )

abnormal long bone epiphyseal plate morphology ( J:69396 )

• the chondrocyte columns are disorganized and premature differentiation to the hypertrophic state occurs

abnormal long bone epiphyseal plate proliferative zone ( J:69396 )

• decreased in size

disorganized long bone epiphyseal plate ( J:69396 )

• the chondrocyte columns are disorganized

premature endochondral bone ossification ( J:69396 )

• premature and inappropriate ossification throughout the endochondral skeleton

respiratory system

respiratory failure ( J:69396 )

growth/size/body

protruding tongue ( J:69396 )

• shortening of the mandible results in protrusion of the tongue

small thoracic cavity ( J:69396 )

• narrow thorax

distended abdomen ( J:69396 )

craniofacial

short mandible ( J:69396 )

domed cranium ( J:69396 )

protruding tongue ( J:69396 )

• shortening of the mandible results in protrusion of the tongue

digestive/alimentary system

protruding tongue ( J:69396 )

• shortening of the mandible results in protrusion of the tongue

Genotype
MGI:3617822

cn2

• Allelic Composition: Pthlh^tm1Ack/Pthlh^tm1Hmk; Tg(LGB-cre)74Acl/0
• Genetic Background: involves: 129 * C57BL/6 * CBA

skeleton

abnormal osteoclast morphology ( J:86536 )

• the osteoclast surface/bone surface ratio and number of osteoclasts per bone perimeter are reduced

increased bone mass ( J:86536 )

• the reduced rate of bone turnover during lactation preserves bone mass so that on day 12 of lactation mutants have nearly 20% more bone mass than controls

• however, bone mass is similar to controls at the start of lactation

abnormal bone ossification ( J:86536 )

• bone formation rate per tissue volume is reduced

• however, osteoblast numbers and surface appear normal

homeostasis/metabolism

abnormal circulating hormone level ( J:86536 )

• plasma levels of parathyroid hormone related protein are significantly lower in lactating mutants compared to controls; however plasma levels of parathyroid hormone and calcium are normal

abnormal vitamin D level ( J:86536 )

• plasma levels of 1,25-dihydroxy vitamin D are significantly lower (43.5 +/- 2.2 pg/ml versus 55.9 +/- 5.9 pg/ml in controls)

abnormal urine homeostasis ( J:86536 )

• urinary excretion of cAMP is decreased to 19.3 +/- 0.8 ug/mmol creatinine compared to 33.9 +/- 0.6 ug/mmol creatinine in controls

• urinary levels of C-telopeptides of type I collagen are significantly lower (3.98 +/- 0.82 ug/mmol creatinine versus 6.83 +/- 0.29 ug/mmol creatinine in controls)

reproductive system

reproductive system phenotype ( J:86536 )

N • no functional defects in lactation, abnormalities in mammary gland morphology, or decrease in litter size or growth of pups is seen

renal/urinary system

abnormal urine homeostasis ( J:86536 )

• urinary excretion of cAMP is decreased to 19.3 +/- 0.8 ug/mmol creatinine compared to 33.9 +/- 0.6 ug/mmol creatinine in controls

• urinary levels of C-telopeptides of type I collagen are significantly lower (3.98 +/- 0.82 ug/mmol creatinine versus 6.83 +/- 0.29 ug/mmol creatinine in controls)

hematopoietic system

abnormal osteoclast morphology ( J:86536 )

• the osteoclast surface/bone surface ratio and number of osteoclasts per bone perimeter are reduced

immune system

abnormal osteoclast morphology ( J:86536 )

• the osteoclast surface/bone surface ratio and number of osteoclasts per bone perimeter are reduced

Genotype
MGI:3617821

cn3

• Allelic Composition: Pthlh^tm1Ack/Pthlh^tm1.1Ack; Tmem163^{Tg(ACTB-cre)2Mrt}/0
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * BALB/c * FVB/N

mortality/aging

neonatal lethality, complete penetrance ( J:69396 )

• phenotype is stated to be identical to that of conditional mutants with a Pthlh^tm1Hmk allele in place of the Pthlh^tm1.1Ack allele; however no data is presented in J:69396

skeleton

short mandible ( J:69396 )

domed cranium ( J:69396 )

abnormal long bone epiphyseal plate morphology ( J:69396 )

abnormal long bone epiphyseal plate proliferative zone ( J:69396 )

premature endochondral bone ossification ( J:69396 )

respiratory system

respiratory failure ( J:69396 )

growth/size/body

protruding tongue ( J:69396 )

• shortening of the mandible results in protrusion of the tongue

small thoracic cavity ( J:69396 )

• narrow thorax

distended abdomen ( J:69396 )

craniofacial

short mandible ( J:69396 )

domed cranium ( J:69396 )

protruding tongue ( J:69396 )

• shortening of the mandible results in protrusion of the tongue

digestive/alimentary system

protruding tongue ( J:69396 )

• shortening of the mandible results in protrusion of the tongue

Genotype
MGI:3617818

cn4

• Allelic Composition: Pthlh^tm1Ack/Pthlh^tm1Ack; Tg(Col1a1-cre)1Ack/0
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * FVB/N

skeleton

abnormal osteoclast morphology ( J:100918 )

• the number and surface of osteoclasts is reduced by 43% and 52%, respectively

decreased osteoclast cell number ( J:100918 )

decreased bone mineral density ( J:100918 )

• long bones appear less radiopaque and bone mineral density is decreased

abnormal osteoblast morphology ( J:100918 )

• osteoblast number and surface are decreased by 55% and 60%, respectively and osteoid volume is decreased by 75%

decreased osteoblast cell number ( J:100918 )

• the percentage of apoptotic osteoblasts/osteocytes is increased more than 8-fold compared to controls

abnormal trabecular bone morphology ( J:100918 )

• the bone marrow space is increased with only scattered thin spicules of trabecular bone trabecular number and thickness are decreased and trabecular separation is increased in the distal femur and proximal tibia

• however, there is no increase in bone marrow adiposity unlike Pthlh null homozygotes

abnormal bone ossification ( J:100918 )

• the mineral apposition rate is decreased by 45% and 60% in the tibial cortex and trabeculae, respectively

hematopoietic system

abnormal osteoclast morphology ( J:100918 )

• the number and surface of osteoclasts is reduced by 43% and 52%, respectively

decreased osteoclast cell number ( J:100918 )

immune system

abnormal osteoclast morphology ( J:100918 )

• the number and surface of osteoclasts is reduced by 43% and 52%, respectively

decreased osteoclast cell number ( J:100918 )