Progressive skeletal defects caused by Kindlin3 deficiency, a model of autosomal recessive osteopetrosis in humans.

ABSTRACT: The cellular and molecular mechanisms of bone development and homeostasis are clinically important, but not fully understood. Mutations in integrins and Kindlin3 in humans known as Leukocyte adhesion deficiencies (LAD) cause a wide spectrum of complications, including osteopetrosis. Yet, the rarity, frequent misdiagnosis, and lethality of LAD preclude mechanistic analysis of skeletal abnormalities in these patients. Here, using inducible and constitutive tissue-specific Kindlin3 knockout (K3KO) mice, we show that the constitutive lack of embryonic-Kindlin3 in myeloid lineage cells causes growth retardation, edentulism, and skull deformity indicative of hydrocephaly. Micro-CT analysis revealed craniosynostosis, choanal stenosis, and micrognathia along with other skeletal abnormalities chara

SUBMITTER: Dudiki T 

PROVIDER: S-EPMC9133165 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature