Phenotypes associated with this allele

• Allele Symbol: Casr^tm1Ces
• Allele Name: targeted mutation 1, Christine Seidman
• Allele ID: MGI:2176758
• Summary: 2 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Casr^tm1Ces/Casr^tm1Ces	involves: 129X1/SvJ * Black Swiss	MGI:2176759
ht2	Casr^tm1Ces/Casr^+	involves: 129X1/SvJ * Black Swiss	MGI:2176761

Genotype
MGI:2176759

hm1

• Allelic Composition: Casr^tm1Ces/Casr^tm1Ces
• Genetic Background: involves: 129X1/SvJ * Black Swiss

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

mortality/aging

postnatal lethality, complete penetrance ( J:29900 , J:71056 )

• most homozygotes are viable at birth but usually die between days 3 and 30 of life (J:29900)

• very few homozygotes survive beyond 7 days of age (J:71056)

behavior/neurological

lethargy ( J:29900 )

• after birth, homozygotes become progressively lethargic

aphagia ( J:29900 )

• homozygotes are unable to feed on standard mouse chow pellets and can rarely be weaned

abnormal postural reflex ( J:29900 )

• homozygotes fail to exhibit normal extension of digits, elbows or knee joints

abnormal posture ( J:29900 )

• mutants are unable to elevate their abdomens from the floor

• when flipped onto their backs, homozygotes are unable to return to an upright position

endocrine/exocrine glands

abnormal parathyroid gland chief cell morphology ( J:29900 )

• diffuse hyperplasia of the parathyroid chief cells

enlarged parathyroid gland ( J:29900 )

parathyroid gland hyperplasia ( J:29900 )

• mutant parathyroid glands display diffuse hyperplasia of the parathyroid chief cells

pigmented parathyroid gland ( J:29900 )

growth/size/body

decreased body size ( J:71056 )

• by P6, homozygotes display a significant reduction in skeletal size

decreased body weight ( J:71056 )

• by P6, homozygotes weigh significantly less than wild-type

postnatal growth retardation ( J:29900 )

• homozygotes display a significant reduction in growth after P2

hematopoietic system

increased hematocrit ( J:29900 )

• the hematocrits of homozygotes are significantly higher than those of heterozygotes or wild-type

homeostasis/metabolism

increased circulating parathyroid hormone level ( J:29900 )

• relative to heterozygotes, homozygotes display significantly increased PTH concentrations (90-fold increase)

increased circulating calcium level ( J:29900 )

• relative to heterozygotes, homozygotes display significantly increased serum Ca2+ concentrations

increased circulating magnesium level ( J:29900 )

• homozygotes display modest elevations of serum Mg2+ concentration

decreased circulating phosphate level ( J:71056 )

• homozygotes show a modest, but significant, reduction in serum inorganic phosphorus

dehydration ( J:29900 )

• in homozygotes, higher hematocrits probably reflect dehydration due to feeding difficulties and/or diuresis induced by hypercalcemia

decreased urine calcium level ( J:29900 )

• the urinary concentration of Ca2+ is abnormally low given the marked elevations in serum Ca2+ levels

renal/urinary system

decreased urine calcium level ( J:29900 )

• the urinary concentration of Ca2+ is abnormally low given the marked elevations in serum Ca2+ levels

skeleton

increased width of hypertrophic chondrocyte zone ( J:71056 )

• homozygotes display a widened zone of hypertrophic chondrocytes in the growth plate

kyphoscoliosis ( J:29900 )

• homozygotes display kyphoscoliosis and bowing of the long bones

decreased bone mineral density ( J:29900 )

• homozygotes frequently exhibit a marked reduction of all bones

abnormal bone mineralization ( J:71056 )

• the dry ashed weight is reduced, consistent with osteopenia due to excess osteoid (unmineralized matrix) accumulation

• homozygotes show impaired mineralization of extracellular matrix in both cortical and trabecular bone, and poor mineralization of cartilage

rickets ( J:71056 )

• unexpectedly, 2- to 6-day-old homozygotes exhibit severe rickets rather than the anticipated PTH-mediated skeletal changes

delayed bone ossification ( J:71056 )

• 2- to 6-day-old newborns display delayed endochondral ossification in the epiphysis and metaphysis of long bones

Genotype
MGI:2176761

ht2

• Allelic Composition: Casr^tm1Ces/Casr⁺
• Genetic Background: involves: 129X1/SvJ * Black Swiss

endocrine/exocrine glands

endocrine/exocrine gland phenotype ( J:29900 )

N • parathyroid glands from heterozygous mutants are of normal size and structure and display normal cell morphology

growth/size/body

growth/size/body region phenotype ( J:29900 )

N • heterozygotes display no differences in physique, body weight or physical activity relative to wild-type

hematopoietic system

hematopoietic system phenotype ( J:29900 )

N • heterozygotes display no differences in the mean hematocrit relative to wild-type

homeostasis/metabolism

increased circulating parathyroid hormone level ( J:29900 )

• despite increased calcium serum levels, heterozygotes show a significant increase in serum parathyroid hormone (PTH) levels

• when fed with Ca2+ contents of 2.5%, 0.6% or 0.02% for 3 weeks, heterozygotes do alter PTH release on response to increases in dietary Ca2+, although the serum calcium concentration associated with a given level of PTH is higher in heterozygotes relative to wild-type

increased circulating calcium level ( J:29900 )

• heterozygotes show a benign elevation in serum Ca2+, both in serum total calcium and serum ionized calcium levels

increased circulating magnesium level ( J:29900 )

• heterozygotes display an elevation in serum Mg2+ levels

decreased urine calcium level ( J:29900 )

• heterozygotes display hypocalciuria relative to wild-type

renal/urinary system

renal/urinary system phenotype ( J:29900 )

N • heterozygous kidneys appear histologically and anatomically normal relative to wild-type

decreased urine calcium level ( J:29900 )

• heterozygotes display hypocalciuria relative to wild-type

skeleton

skeleton phenotype ( J:29900 )

N • heterozygotes do not display any skeletal abnormalities

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
familial hypocalciuric hypercalcemia 1		DOID:0060700	OMIM:145980	J:29900