Phenotypes associated with this allele

• Allele Symbol: Gcm2^tm1Kry
• Allele Name: targeted mutation 1, Gerard Karsenty
• Allele ID: MGI:1889069
• Summary: 2 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Gcm2^tm1Kry/Gcm2^tm1Kry	involves: 129S7/SvEvBrd	MGI:3588582
hm2	Gcm2^tm1Kry/Gcm2^tm1Kry	involves: 129S7/SvEvBrd * C57BL/6J	MGI:3722781

Genotype
MGI:3588582

hm1

• Allelic Composition: Gcm2^tm1Kry/Gcm2^tm1Kry
• Genetic Background: involves: 129S7/SvEvBrd

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

mortality/aging

perinatal lethality, incomplete penetrance ( J:63291 )

• 30% die shortly after birth due to severe hypocalcemia

• lethality of homozygous pups increases considerably when homozygous females are used in matings, indicating that the lethality is of maternal orgin, probably due to low extracellular calcium concentration in females and decreased milk production, as treatment with vitamin D to correct calcium levels, paritally rescues the lethality

endocrine/exocrine glands

absent parathyroid glands ( J:63291 )

decreased activity of parathyroid ( J:63291 )

• exibit biological hypoparathyroidism as parathyroid glands are absent, however parathyroid hormone serum levels are normal, indicating another source of this hormone

homeostasis/metabolism

decreased circulating calcium level ( J:63291 , J:78067 )

• mice with severe hypocalcemia die shortly after birth, while the remaining mice exhibit mild hypocalcemia (J:63291)

decreased circulating phosphate level ( J:63291 )

increased urine calcium level ( J:63291 )

• increased calcium elimination in the urine without evidence of renal failure

skeleton

abnormal trabecular bone morphology ( J:63291 )

• increased number and thickness of trabeculae

increased bone mass ( J:63291 )

abnormal bone ossification ( J:63291 )

• decreased osteoblast and osteoclast surface

renal/urinary system

increased urine calcium level ( J:63291 )

• increased calcium elimination in the urine without evidence of renal failure

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
hypoparathyroidism		DOID:11199		J:63291

Genotype
MGI:3722781

hm2

• Allelic Composition: Gcm2^tm1Kry/Gcm2^tm1Kry
• Genetic Background: involves: 129S7/SvEvBrd * C57BL/6J

craniofacial

abnormal third pharyngeal arch morphology ( J:121311 )

• at E12, apoptosis is detected in the region of the endoderm where the primordium is separating from the pharyngeal pouch (presumptive parathyroid domain) in contrast to no or few apoptotic cells in wild-type embryos

embryo

abnormal third pharyngeal arch morphology ( J:121311 )

• at E12, apoptosis is detected in the region of the endoderm where the primordium is separating from the pharyngeal pouch (presumptive parathyroid domain) in contrast to no or few apoptotic cells in wild-type embryos

endocrine/exocrine glands

abnormal parathyroid gland development ( J:121311 )

• initial specification occurs but apoptosis of parathyroid domain tissue occurs between E12-12.5; parathyroid differentiation starts but is blocked by Gcm2 deletion and markers for parathyroid such as Pth mRNA and protein are absent after E12.5

absent parathyroid glands ( J:121311 )

• parathyroid glands are absent from mutants