mortality/aging
• homozygotes develop to term; however, about 50% die before weaning
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hematopoietic system
• homozygotes display progressively increased red blood cell counts relative to wild-type mice (10.4 0.1 106/mm3 vs 9.7 0.1 106/mm3, respectively)
|
• homozygotes display progressively increased hematocrits relative to wild-type mice (53.6 0.9 vs 49.9 1.0, respectively)
|
• homozygotes display progressively increased hemoglobin levels relative to wild-type mice (16.7 0.2 g/dl vs 15.6 0.2 g/dl, respectively)
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• the number and size of osteoclasts in cultures of bone marrow cells from 2-month-old homozygotes are ~2x that of wild-type
|
homeostasis/metabolism
• in homozygotes, the half life of [125I]ANP in circulation is two-thirds longer than in wild-type mice, although plasma levels of both atrial and B-type natriuretic peptides (ANP and BNP) remain relatively unaffected
|
• at 2 months, homozygotes exhibit a 150% increase in plasma alkaline phosphatase levels relative to wild-type mice
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dehydration
(
J:56058
)
• homozygotes appear dehydrated shortly after birth
|
• homozygotes exhibit a >300% increase in total daily excretion of cGMP in the urine relative to wild-type mice
|
• homozygotes can excrete dilute urine after water loading but are progressively and significantly less able than wild-type mice to concentrate urine; however, no shortening of the renal papilla is observed
|
cardiovascular system
hypovolemia
(
J:56058
)
• homozygotes exhibit reduced intravascular blood volume relative to wild-type mice
|
hypotension
(
J:56058
)
• in homozygotes, blood pressures are reduced by 8 mmHg relative to wild-type mice (110.4 2.3 mmHg vs 118.7 1.9 mmHg, respectively)
|
renal/urinary system
• homozygotes exhibit a >300% increase in total daily excretion of cGMP in the urine relative to wild-type mice
|
• homozygotes can excrete dilute urine after water loading but are progressively and significantly less able than wild-type mice to concentrate urine; however, no shortening of the renal papilla is observed
|
• homozygotes exhibit no significant differences in plasma Na+, K+, Ca2+, Cl-, creatinine, and urea nitrogen concentrations or in daily urinary excretion of Na+, K+, Cl-, creatinine, or protein relative to wild-type mice
• however, homozygotes display a mild progressive increase in total daily urine output relative to wild-type littermates
|
behavior/neurological
polydipsia
(
J:56058
)
• homozygotes tend to display a progressive increase in water intake
|
• at P7, homozygotes display hunched backs
|
growth/size/body
• at P7, homozygotes display decreased body weight relative to wild-type mice
|
• at P7, homozygotes display increased body length relative to wild-type mice
|
skeleton
domed cranium
(
J:56058
)
• at P7, homozygotes display dome-shaped skulls
|
• the number and size of osteoclasts in cultures of bone marrow cells from 2-month-old homozygotes are ~2x that of wild-type
|
• at P7, homozygotes display elongated femurs and tibias relative to wild-type mice
|
• at P7, homozygotes display elongated metatarsal and digital bones relative to wild-type mice
|
• adult homozygotes exhibit small thoracic cages relative to wild-type mice
|
• at P7, homozygotes display longer vertebral bodies than wild-type mice
|
• the number of osteoblastic precursors from 2-month-old homozygotes is ~3 that of wild-type, and they proliferate almost twice as rapidly
|
• in young homozygotes, bony trabeculae appear thicker and longer than normal
|
• at P10, cellular expansion is apparent in the zone of hypertrophic chondrocytes but not in the zones with resting or proliferating chondrocytes; however, this difference is no longer observed at 3 months
|
• at P10, homozygotes display delayed development of secondary ossification centers in their long bones
|
• at 2 months, homozygotes (but not heterozygotes) exhibit increased bone turnover, as shown by a 150% increase in plasma alkaline phosphatase (an indicator of bone formation) and a >200% increase in urinary pyridonoline and deoxypyridonoline (indicators of bone resorption)
|
craniofacial
domed cranium
(
J:56058
)
• at P7, homozygotes display dome-shaped skulls
|
limbs/digits/tail
• at P7, homozygotes display elongated metatarsal and digital bones relative to wild-type mice
|
• at P7, homozygotes exhibit elongated tails that, in some mice, appear initially wavy
|
reproductive system
• only one third of surviving homozygotes reproduce at least once
|
immune system
• the number and size of osteoclasts in cultures of bone marrow cells from 2-month-old homozygotes are ~2x that of wild-type
|