Home About Browse Search
Svenska


Hmga2 deficiency is associated with allometric growth retardation, infertility, and behavioral abnormalities in mice

Lee, Mi Ok and Li, Jingyi and Davis, Brian W. and Upadhyay, Srijana and Al Muhisen, Hadil M. and Suva, Larry J. and Clement, Tracy M. and Andersson, Leif (2022). Hmga2 deficiency is associated with allometric growth retardation, infertility, and behavioral abnormalities in mice. G3. 12 :2 , jkab417
[Research article]

[img] PDF
854kB

Abstract

The high mobility group AT-hook 2 (HMGA2) protein works as an architectural regulator by binding AT-rich DNA sequences to induce conformational changes affecting transcription. Genomic deletions disrupting HMGA2 coding sequences and flanking noncoding sequences cause dwarfism in mice and rabbits. Here, CRISPR/Cas9 was used in mice to generate an Hmga2 null allele that specifically disrupts only the coding sequence. The loss of one or both alleles of Hmga2 resulted in reduced body size of 20% and 60%, respectively, compared to wild-type littermates as well as an allometric reduction in skull length in Hmga2(-/-) mice. Both male and female Hmga2(-/-) mice are infertile, whereas Hmga2(+/-) mice are fertile. Examination of reproductive tissues of Hmga2(-/-) males revealed a significantly reduced size of testis, epididymis, and seminal vesicle compared to controls, and 70% of knock-out males showed externalized penis, but no cryptorchidism was observed. Sperm analyses revealed severe oligospermia in mutant males and slightly decreased sperm viability, increased DNA damage but normal sperm chromatin compaction. Testis histology surprisingly revealed a normal seminiferous epithelium, despite the significant reduction in testis size. In addition, Hmga2(-/-) mice showed a significantly reduced exploratory behavior. In summary, the phenotypic effects in mouse using targeted mutagenesis confirmed that Hmga2 is affecting prenatal and postnatal growth regulation, male reproductive tissue development, and presents the first indication that Hmga2 function is required for normal mouse behavior. No specific effect, despite an allometric reduction, on craniofacial development was noted in contrast to previous reports of an altered craniofacial development in mice and rabbits carrying deletions of both coding and noncoding sequences at the 5 ' part of Hmga2.

Authors/Creators:Lee, Mi Ok and Li, Jingyi and Davis, Brian W. and Upadhyay, Srijana and Al Muhisen, Hadil M. and Suva, Larry J. and Clement, Tracy M. and Andersson, Leif
Title:Hmga2 deficiency is associated with allometric growth retardation, infertility, and behavioral abnormalities in mice
Series Name/Journal:G3
Year of publishing :2022
Volume:12
Number:2
Article number:jkab417
Number of Pages:8
Publisher:OXFORD UNIV PRESS INC
ISSN:2160-1836
Language:English
Publication Type:Research article
Article category:Scientific peer reviewed
Version:Published version
Copyright:Creative Commons: Attribution 4.0
Full Text Status:Public
Subjects:(A) Swedish standard research categories 2011 > 1 Natural sciences > 106 Biological Sciences (Medical to be 3 and Agricultural to be 4) > Genetics (medical genetics to be 30107 and agricultural genetics to be 40402)
(A) Swedish standard research categories 2011 > 1 Natural sciences > 106 Biological Sciences (Medical to be 3 and Agricultural to be 4) > Developmental Biology
Keywords:high mobility group AT-hook 2, CRISPR, Cas9, sterility, behavior
URN:NBN:urn:nbn:se:slu:epsilon-p-116598
Permanent URL:
http://urn.kb.se/resolve?urn=urn:nbn:se:slu:epsilon-p-116598
Additional ID:
Type of IDID
DOI10.1093/g3journal/jkab417
Web of Science (WoS)000768242900016
ID Code:27607
Faculty:VH - Faculty of Veterinary Medicine and Animal Science
Department:(VH) > Dept. of Animal Breeding and Genetics
Deposited By: SLUpub Connector
Deposited On:25 Apr 2022 08:25
Metadata Last Modified:25 Apr 2022 08:31

Repository Staff Only: item control page

Downloads

Downloads per year (since September 2012)

View more statistics

Downloads
Hits