# EMBRYOLOGIC CONSEQUENCES OF TRISOMY 16 IN MICE

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA RIVERSIDE · 1994 · $152,192

## Abstract

The long term objective of this research program remains the analysis of
the developmental consequences of overexpression of genes triplicated in
the trisomy 16 (Ts16) mouse.  Two such genes located on mouse chromosome
16 (MMU 16) encode preprosomatostatin (Smst) and a transcription factor,
pit-1 (dwarf, dw).  Although dwarf and Smst are not the same gene, dwarf
mice express elevated levels of preprosomatostatin in various regions of
their brains, and have premature loss of Smst expressing cells in regions
of their hypothalami.  The overall aims of this proposal are to determine
whether the products of the Smst gene function to modulate growth and/or
development and survival of neurons and glia in the early nervous system
in normal, Ts16, and dwarf mice and thus to contribute to the structural
and neurochemical deficits observed in Ts16 mice and dwarf mice.  to
dissect the neurobiological effects of excess somatostatin expression
independent of the effects that arise from triplication of the dwarf
locus in Ts16 mice, mice transgenic for the endogenous Smst gene will
also be studied.  Five separate lines of such Smst transgenic (SmstTg)
mice have been developed, and differ in genetic background, levels of
overexpression, and phenotype.  Three of these SmstTg lines have been
well characterized and exhibit both intrauterine and postnatal growth
alterations and variable levels of overexpression of Smst in different
regions of their brains.  One line, SmstTg13, exhibits intrauterine and
postnatal growth retardation, excess Smst expression, increased levels
of proSRIF derived peptides, and cholinergic deficits, reminiscent of the
phenotype of the dwarf mouse.

The first specific aim is to characterize Smst expression in early brain
development in normal, Ts16, Smst transgenic, and dwarf mice, and to
correlate such expression with parameters of growth during the prenatal
and postnatal period.  The second specific aim is to examine the
generation and survival of cholinergic neuron populations in the brain
and spinal cord of these groups of mice relative to levels of Smst
expression.  The third specific aim is to analyze particular behavioral
and neurochemical changes which occur in normal, SmstTg, and dwarf mice
during the postnatal period, particularly changes which occur in
spontaneous activity and in the parameters of the cholinergic system.
Methods for RNA and DNA analysis and quantification, polymerase chain
reaction and reverse transcription polymerase chain reaction, in situ
hybridization, radioimmunoassay, immunocytochemistry, single pulse and
cumulative cell birthdating, and light and electron microscopy will be
used in these studies.  Together, these studies will help us to obtain
a greater understanding of the role of somatostatin in normal and
abnormal development of the nervous system and the relationship between
smst expression and the expression of the transcription factor, pit-1.

## Key facts

- **NIH application ID:** 2197901
- **Project number:** 5R01HD019932-07
- **Recipient organization:** UNIVERSITY OF CALIFORNIA RIVERSIDE
- **SAM.gov UEI:** MR5QC5FCAVH5
- **Principal Investigator:** Mary L Oster-Granite
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1994
- **Award amount:** $152,192
- **Award type:** 5
- **Project period:** 1984-07-01 → 1996-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/2197901

## Citation

> US National Institutes of Health, RePORTER application 2197901, EMBRYOLOGIC CONSEQUENCES OF TRISOMY 16 IN MICE (5R01HD019932-07). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/2197901. Licensed CC0.

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