Mouse Genome Informatics
hm1
    Alpltm1Jlm/Alpltm1Jlm
either: (involves: 129S2/SvPas) or (involves: 129S2/SvPas * C57BL/6J)
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• mice die before weaning, on average at 8-10 days of age

growth/size/body
• animals have almost no body fat
• most mutants become progressively exhausted and body weights are only 30-50% of controls at the time of death

homeostasis/metabolism
• most neonates and embryos (E9.5 and E18.5) do not have any detectable alkaline phosphatase activity in the serum, although about 30% of neonates do have low levels

adipose tissue
• animals have almost no body fat

behavior/neurological
• poor coordination and mutants appear disoriented
• 9-10 day old mutants fall off a small box much quicker than controls and when placed on inclined planes, they do not distinguish if they are placed facing upwards or downwards on the slope like wild-type which always move up the slope
• animals became progressively exhausted
• about 50% of mutants exhibit severe epileptic seizures 1-2 days before their death
• seizures appear as constant running in the cage, high-pitched vocalizations, biting of the tongue, and loss of consciousness in a supine position associated with apnea for periods of 30 sec or more

digestive/alimentary system
• large amounts of gas in small intestines
• small intestine contains large amount of gas, suggesting impaired intestinal movement

hematopoietic system
• thinner thymus cortex
• the cortex of the thymus contains many basophilic necrotic apoptotic cells
• WBC count is reduced to 58.3% of wild-type
• spleen exhibits a reduction in cell mass in the outer layer and an altered ratio of red to white pulp

immune system
• thinner thymus cortex
• the cortex of the thymus contains many basophilic necrotic apoptotic cells
• WBC count is reduced to 58.3% of wild-type
• spleen exhibits a reduction in cell mass in the outer layer and an altered ratio of red to white pulp

muscle
• reduction in muscle structure

respiratory system
• bleeding in lung tissue is observed in some mutants that have a severe seizure attack and die
• occurs in conjunction with the epileptic seizures

nervous system
• about 50% of mutants exhibit severe epileptic seizures 1-2 days before their death
• seizures appear as constant running in the cage, high-pitched vocalizations, biting of the tongue, and loss of consciousness in a supine position associated with apnea for periods of 30 sec or more
• bleeding in the cranial ventricle is observed in some mutants that have a severe seizure attack and die
• nerve roots emerging from the spinal cord and descending within the dura are thinner than in controls
• reduction in nerve root mass; not due to increased cell death

cardiovascular system
• 50% of mutants that died after severe seizure attacks showed bleeding in the thoracic cavity
• bleeding in lung tissue is observed in some mutants that have a severe seizure attack and die
• bleeding in the cranial ventricle is observed in some mutants that have a severe seizure attack and die

craniofacial
• thin parietal bones

skeleton
• thin parietal bones
• shorter growth plates in the metaphysis of P11 mutants
• metaphysis contains excessive number of erythroctyes
• osteoblasts with abnormal morphology are seen on the surfaces of trabeculae and in the periosteal region of the diaphysis
• up to 50% of mature osteoblasts in the parietal bones contain abnormal vacuoles
• poor mineralization in the parietal bones, scapulae, vertebral bones, and ribs at P8
• observe evidence of spontaneous fractures in the fibulae

endocrine/exocrine glands
• thinner thymus cortex
• the cortex of the thymus contains many basophilic necrotic apoptotic cells

Mouse Models of Human Disease
OMIM IDRef(s)
Hypophosphatasia, Infantile 241500 J:39015


Mouse Genome Informatics
hm2
    Alpltm1Jlm/Alpltm1Jlm
involves: 129S2/SvPas * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
skeleton
• phosphate and calcium deposition in bone is decreased compared to in wild-type mice
• calvarial osteoblasts from smaller mineralized nodules compared with Alpltm1Jlm homozygous cells


Mouse Genome Informatics
cn3
    Alpltm1Jlm/Alpl+
Phospho1m1Jlm/Phospho1m1Jlm

involves: 129S2/SvPas * C3HeB/FeJ * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• fewer than expected mice are born

skeleton
• at the site of fractures
• prominent at P10
• secondary ossification centers are smaller and less developed than in Phospho1m1Jlm homozygotes
• mice exhibit reduced bone mineralization compared with Phospho1m1Jlm homozygotes
• mice exhibit osteoidosis unlike wild-type mice
• prominent at P10

limbs/digits/tail
• at the site of fractures


Mouse Genome Informatics
cx4
    Alpltm1Jlm/Alpltm1Jlm
Spp1tm1Rit/Spp1tm1Rit

involves: 129S2/SvPas * 129S7/SvEvBrd * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• mice die within 10 to 14 days of birth

skeleton
• mineral deposition is decreased compared to in wild-type mice
• bone marrow density and bone volume fraction in thoracic vertebrae are increased compared to in Alpltm1Jlm homozygotes
• bone marrow density and bone volume fraction in lumbar vertebrae are increased compared to in wild-type mice
• bone volume fraction in lumbar vertebrae are increased compared to in wild-type mice and Spp1tm1Rit homozygotes
• trabecular number is greater than in Alpltm1Jlm homozygotes and wild-type mice
• calvarial osteoblasts form larger mineralized nodules compared with Alpltm1Jlm homozygous cells

growth/size/body


Mouse Genome Informatics
cx5
    Alpltm1Jlm/Alpltm1Jlm
Phospho1m1Jlm/Phospho1m1Jlm

involves: 129S2/SvPas * C3HeB/FeJ * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• while normal numbers of mice are present at E16.5, only one stillborn mouse is observed from multiple matings

skeleton
• at E16.5, mice exhibit a complete lack of skeletal mineralization of bone and cartilage compared with wild-type mice
• at E16.5, calcification of vertebral bones and femur is reduced compared to in wild-type mice
• the one stillborn mouse produced lacked mineralization in the appendicular skeleton and exhibit partial mineralization of the axial skeleton and craniofacial bones compared with wild-type mice